This study was conducted to evaluate the safety profile of Pantohematogen, a substance derived from the velvet antlers of the Altai Wapiti, which is commonly used as a functional ingredient in dietary supplements. In this clinical research, both male and female Wistar rats received the maximum tolerable intragastric dose of Pantohematogen. Over the course of six months, researchers monitored the animals for changes in general health status, body mass, hematologic and bone marrow parameters, and the functioning of major organs, including the liver, kidneys, heart, and brain.
Throughout the experimental period, the animals exhibited stable behavior and maintained normal fur condition, appetite, reflex responses, and gastrointestinal and urinary tract function. No signs of a toxic response were detected following intragastric administration. However, administration of Pantohematogen at 250 and 500 mg/kg resulted in increased liver mass and reduced testicular size in male rats. This condition persisted for 2 weeks after treatment cessation. Other internal organs showed no abnormalities when compared with control and untreated animals.
Importantly, the tested doses exceeded standard human-equivalent levels (per kilogram of body weight) by factors of 2, 10, and 20, respectively. Despite this, the findings indicated no evident toxicological impact from Pantohematogen exposure. This research was conducted at the Tomsk National Research Medical Center of the Russian Academy of Sciences under the supervision of Dr. N.I. Suslov, Doctor of Medical Science.
Antler-derived compounds are extensively incorporated into various dietary supplements due to their reputed adaptogenic effects [1–6]. Among these, Pantohematogen, extracted from the velvet antlers of the Altai Wapiti, has witnessed a surge in use [1, 7–14]. The objective of this clinical research was to assess the safety of Pantohematogen under experimental conditions.
This investigation was carried out at the Tomsk National Research Medical Center of the Russian Academy of Sciences, under the direction of Dr. N.I. Suslov, Doctor of Medical Science, is overseeing the project.
To evaluate the systemic impact of Pantohematogen, a six-month trial was conducted on male and female Wistar rats. The scope included observations on physical health, changes in body mass, hematological indices, bone marrow morphology, liver and kidney function, and performance of both cardiovascular and central nervous systems [15, 16]. The Pantohematogen preparation was administered intragastrically [17, 18].
Standard vivarium conditions were maintained for both Wistar rats (170–240 g, 5 males and 5 females) and CBA mice (5 males and 5 females) during the trials. The test material consisted of the finished Pantohematogen dosage form, which was pulverized and combined with a 1% starch base for administration.
A single 5000 mg/kg dose of Pantohematogen, mixed at a 1:4 ratio with the starch solution, was administered intragastrically to the rats. Over a 14-day surveillance period, no abnormalities were noted. The subjects retained typical behavior, coat condition, food intake, reflex responses, and intact excretory and digestive functions. No toxicological symptoms were evident following high-dose exposure.
Similarly, CBA mice were given 5000 mg/kg of the same solution, delivered in two portions to avoid exceeding the permissible intragastric volume. While the first day showed decreased activity and reduced appetite, sneezing and disheveled fur appeared on Days 2 and 3. By Day 6, these symptoms resolved, and the mice remained clinically stable for the remainder of the observation period.
A second group of CBA mice received 10000 mg/kg in three divided doses on a single day. The early post-administration phase showed greater suppression of appetite and movement than the 5000 mg/kg group. Sneezing and poor coat condition persisted through Days 2 to 6. However, there were no fatalities or signs of enduring toxicity throughout the two-week observation. Due to the absence of lethal outcomes, the LD50 value could not be calculated.
The findings suggest that Pantohematogen may be classified as a low-risk substance (Class 4 according to GOST 12.1.007-76), indicating a relatively non-toxic profile.
For long-term toxicity evaluation, 130 Wistar rats (an equal number of males and females) were assigned to experimental groups. The administered formulation included 10 parts Pantohematogen, 20 parts glucose, and 1 part ascorbic acid. Subjects were divided as follows:
· Group 1 (effective dose): 155 mg/kg total (containing 50 mg/kg Pantohematogen)
· Group 2 (intermediate dose): 775 mg/kg total (containing 250 mg/kg Pantohematogen)
· Group 3 (maximum dose): 1550 mg/kg total (containing 500 mg/kg Pantohematogen)
Control animals received a reference solution composed of 20 parts glucose and 1 part ascorbic acid at a concentration of 21% (1050 mg/kg). Both test and control groups were administered their respective preparations daily for a continuous six-month period (Table 1).
Table 1. Groups and doses
Group | Dose (pantohematogen content) | Males | Females |
Group 1 | 50 mg/kg | 15 | 15 |
Group 2 | 250 mg/kg | 15 | 15 |
Group 3 | 500 mg/kg | 15 | 15 |
Control | Control solution | 10 | 10 |
Intact | Intact animals | 10 | 10 |
Throughout the study, comprehensive monitoring was conducted to track changes in overall well-being, body mass, peripheral blood parameters, bone marrow composition, hepatic and renal function, and cardiovascular and central nervous system performance [19, 20]. A detailed morphological assessment was also performed on a range of internal organs, including the lungs, kidneys, brain, heart, spleen, thymus, adrenal glands, lymphatic nodes, gonads, and the entire gastrointestinal system [21, 22].
Rats from experimental groups 1, 2, and 3 underwent evaluations at two distinct intervals—once at the 3-month mark and again at 6 months following the initiation of treatment—with a final follow-up conducted two weeks after treatment cessation (6.5 months). For comparison, animals in the control group were assessed at 3 and 6 months, while those in the intact group were evaluated at 3 and 6.5 months. Statistical interpretation of the findings was conducted using the Student’s t-test to determine the significance of observed differences.
Throughout the six months of intragastric pantohematogen administration, no adverse effects were observed in behavior, appetite, coat condition, mucosal surfaces, or pupil appearance. Rats were weighed weekly for the initial three months and biweekly thereafter. Among female rats in groups 1, 2, and 3, weight changes did not differ significantly from those in the control or intact groups. However, male rats in group 3 (500 mg/kg of pantohematogen) demonstrated a 1.5- to 2-fold greater weight gain than male rats in groups 1 and 2, as well as the control and intact groups. No deaths occurred during the study.
Peripheral blood was collected from the tail vein and evaluated using standard hematological techniques to determine hemoglobin levels, erythrocyte, reticulocyte, platelet, and leukocyte counts, along with leukogram profiling. Erythrocyte osmotic resistance to hemolysis was also examined. The hemolysis rate was assessed by quantifying hemoglobin in the supernatant after incubating erythrocytes (0.04 ml citrated blood) in 0.2 ml of 6.5 percent NaCl solution for 60 minutes. Following centrifugation at 1500 rpm for 5 minutes and refrigeration for 48 hours, 0.08 ml of the supernatant was blended with 3 ml of the transforming solution. Hemoglobin content was measured via a GF-C-104 haemoglobinometer at wavelengths between 325 and 500 nm. Blood samples from all experimental (50, 250, and 500 mg/kg of pantohematogen), control (glucose and ascorbic acid in a 20:1 ratio), and intact groups were analyzed.
In male rats from the control group, leukocyte counts—particularly lymphocytes—were elevated in comparison to intact animals. Conversely, female rats from the control group showed reduced hemoglobin levels. Male rats in group 1 exhibited lower hemoglobin and erythrocyte counts than those in the intact group. In group 2 males, reductions in reticulocyte and leukocyte counts were observed compared to controls. In female rats in group 1, hemoglobin levels were lower, whereas monocyte and lymphocyte counts were higher than in both the control and intact groups. These variations remained within normal biological limits and did not correlate with dosage.
Male rats in group 1 showed higher hemoglobin and erythrocyte values than both control and intact animals. Reticulocyte counts in groups 1 and 2 males were lower, though this was not associated with dosage, as control and intact animals had higher initial levels. The rise in osmotic resistance seen in both sexes of the experimental groups was temporary and unrelated to dose, normalizing within two weeks post-administration (6.5 months).
Group 3 rats showed elevated segmented neutrophil counts compared with intact counterparts, whereas group 2 males demonstrated eosinopenia and monocytosis. By 6.5 months, all parameters fell within reference ranges. Changes noted in females were also dose-independent and returned to normal by the end of the observation period. The cause of the neutrophilia-related leukocytosis seen in group 3 males at 6.5 months and the lymphocytosis-linked leukocytosis in group 3 females at 6 months remains uncertain. Overall, while specific peripheral blood parameters fluctuated during prolonged daily administration of pantohematogen (50, 250, and 500 mg/kg), these effects were temporary and non-dose-dependent, indicating no hematological toxicity from the tested doses.
Quantitative assessment of bone marrow cellularity was performed by determining the total karyocyte count per femur, averaging 10 million cells. Bone marrow smears were prepared from sternal segments using a homogenate mixed with autologous serum in a 1:1 ratio, followed by staining via Nocht and Maksimov techniques. Evaluations were conducted at the 3- and 6-month marks during pantohematogen (Groups 1, 2, and 3) and control solution administration, and 2 weeks after cessation at 6.5 months.
At both 3 and 6 months, most hematopoietic indices in the bone marrow did not show statistically significant differences between intact animals and those in the control group. However, a noteworthy exception at 3 months was the increased representation of erythroid precursors in female control rats compared to the intact cohort. This finding normalized but remained within physiological bounds at 6 months.
At 6 months, female control group rats exhibited elevated immature granulocyte counts relative to intact animals, whereas male counterparts showed increased monocyte and lymphocyte levels. In group 3, female rats demonstrated a reduction in erythroid lineage cell numbers and an increase in mature neutrophils, particularly the stab and segmented forms, compared with both the control and intact groups. Additionally, a decline in eosinophils was observed in male rats relative to intact animals. Female rats in this group also exhibited a greater frequency of immature granulocytes than those in the control and intact groups. Across all groups, female rats showed a general reduction in erythroid lineage cells compared with intact counterparts.
At 6.5 months, erythroid nuclear cell counts had normalized. Male rats in group 3 displayed higher levels of nucleated erythrocytes than both the control and intact groups at the 6-month time point. Elevated lymphocyte counts were found in males across all experimental groups, while other deviations remained minor and lacked consistent patterns. These observations suggest that hematopoietic fluctuations in bone marrow during prolonged pantohematogen exposure were short-term and resolved after treatment. Therefore, six months of administration, even at varying doses, does not exert a toxicological burden on bone marrow.
Behavioral assessments were conducted at 3, 6, and 6.5 months using the Open Field test to monitor anxiety and exploratory tendencies in male and female rats, with groups evaluated independently. The test was conducted in a 100x100x60 cm square maze featuring 16 equally spaced floor segments and centrally drilled holes (6 cm in diameter), illuminated from above by a 100-watt lamp positioned 1 meter overhead. Each subject was placed in a maze corner, and observations over 2 minutes included metrics such as grid crossings, hole-poking, vertical rearing, self-grooming, and fecal output.
To complement these data, a semi-quantitative scoring system assessed the animals’ reactions to being caught in their home environment, on a flat surface, and when approached with forceps. Scoring accounted for physiological and behavioral responses—defecation, urination, vocalization, and muscular rigidity—ranging from 1 to 4 points, which were summed to generate an emotional response index. Group comparisons were statistically evaluated using the null hypothesis framework.
Behavioral alterations were observed in animals subjected to pantohematogen, with differences by sex and increasing over time. At the 3-month interval, males in group 3 displayed heightened emotional reactivity, while those in group 2 showed increased physical activity. Among females, similar patterns were seen, though the most evident changes occurred exclusively in group 2.
By 6 months, a modest increase in locomotor output was observed in group 3 males, while their emotional responses were similar to those of the control group. Conversely, group 3 females registered a reduction in emotional responses. At the 6.5-month follow-up, group 2 males showed a dampened emotional response without concurrent changes in physical activity, whereas female behavior was indistinguishable from controls.
These results suggest that the initial trimester of pantohematogen intake may amplify both emotional responsiveness and activity levels. However, with continued use, such activity trends decline and eventually stabilize near baseline, while emotional responsiveness in males may actually diminish.
Biochemical evaluation of hepatic performance encompassed analysis of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total protein levels. Blood glucose measurements assessed hepatic involvement in carbohydrate metabolism, and nitrogen balance was monitored by quantifying serum urea and creatinine levels.
To probe hepatic detoxification pathways and microsomal oxidation, non-inhalational barbiturates metabolized by the liver—specifically Hexobarbital and Thiopental—were utilized. A Hexobarbital Sleep Test was implemented using an 80 mg/kg dose of 1% Hexobarbital solution.
At both 3 and 6 months, male rats in groups 1 and 2 exhibited shortened sleep durations following Hexobarbital administration, indicative of enhanced hepatic enzymatic function. In contrast, extended sleep times were recorded in Group 2 female rats at the 6-month point. Notably, two weeks post-administration, sleep duration in all experimental animals approximated that of the control and intact groups. During the initial 3 months, blood chemistry remained stable, with no significant abnormalities (Table 2).
Table 2. Blood biochemical parameters
Groups and doses | Males | Females |
At 3 months | ||
Intact animals | 31.25 ± 7.33 | 116.20 ± 8.82 |
The control group | 31.80 ± 2.89 | 106.60 ± 11.99 |
Group 1 (50 mg/kg) | 28.80 ± 3.67 | 122.20 ± 5.13 |
Group 2 (250 mg/kg) | 15.00 ± 6.16 | 129.20 ± 1.53 |
Group 3 (500 mg/kg) | 26.75 ± 5.56 | 119.80 ± 2.40 |
At 6 months | ||
Intact animals | 39.00 ± 2.26 | 89.60 ± 6.10 |
The control group | 31.80 ± 2.89 | 93.80 ± 5.28 |
Group 1 (50 mg/kg) | 26.20 ± 3.37 | 99.00 ± 8.33 |
Group 2 (250 mg/kg) | 40.20 ± 3.23 | 113.00 ± 6.17 |
Group 3 (500 mg/kg) | 35.50 ± 0.50 | 85.60 ± 3.92 |
Two weeks after the end of the administration | ||
Intact animals | 39.00 ± 2.26 | 89.60 ± 6.10 |
The control group | 31.80 ± 2.89 | 93.80 ± 5.28 |
Group 1 (50 mg/kg) | 32.40 ± 1.12 | 98.00 ± 21.97 |
Group 2 (250 mg/kg) | 38.00 ± 3.00 | 96.48 ± 13.94 |
Group 3 (500 mg/kg) | 39.80 ± 3.35 | 95.00 ± 12.33 |
By the sixth month of the study, male rats in group 3 exhibited elevated aspartate aminotransferase (AST) levels compared with the control group. Notably, alanine aminotransferase (ALT) levels increased significantly in Groups 1 and 2 compared with intact animals. Additionally, while some experimental groups showed increased blood glucose levels, concurrent declines in urea and creatinine levels were observed. It is important to emphasize that female rats demonstrated greater physiological stability under pantohematogen exposure, showing less pronounced alterations than their male counterparts. At 6.5 months, two weeks after cessation of pantohematogen administration, biochemical markers in the blood of all experimental groups closely matched those of the control group and intact animals. Overall, any fluctuations in blood biochemistry observed during the monitoring period were minimal and transient, and did not show a consistent relationship with dosage. Consequently, prolonged administration of pantohematogen at doses of 50, 250, and 500 mg/kg over 6 months did not elicit hepatotoxicity.
Renal function was assessed using a range of parameters, including total urine volume, pH, urinary protein content, creatinine, glucose, and urea. To ensure accurate urine collection, the animals were housed individually for 24 hours, during which water consumption was controlled at 2% of their body weight. Across all groups, urinary protein levels remained within physiological norms, not exceeding 0.3 g/l, and urine pH values stayed within the reference range, as outlined in Table 3.
Table 3. The kidney function at 3 months (X ± m)
Parameters | Doses (mg/kg) | ||||
| 50 | 250 | 500 | Control | Intact |
Males | |||||
рН | 6-7 | 6-7 | 6-7 | 6-8 | 5-7 |
Daily urine production (ml) | 13.80 ± 0.78 | 15.05 ± 0.60 | 11.12 ± 9.66 | 10.18 ± 1.17 | 13.50 ± 1.44 |
Creatinine (µmol/ml) | 2.00 ± 0.11 | 3.30 ± 0.31 | 5.15 ± 0.63 | 3.39 ± 1.18 | 4.76 ± 0.34 |
Creatinine (µmol/day) | 27.63 ± 2.20 | 47.28 ± 7.30 | 56.49 ± 5.97 | 30.52 ± 7.32 | 63.20 ± 4.27 |
Urea (mol/l) | 102.1 ± 11.1 | 145.2 ± 18.5 | 151.0 ± 29.9 | 141.7 ± 30.2 | 91.9 ± 6.7 |
Urea (mol/day) | 1.41 ± 0.17 | 2.20 ± 0.32 | 1.81 ± 0.31 | 1.36 ± 0.22 | 1.23 ± 0.11 |
Females | |||||
рН | 6-7 | 6-7 | 6-7 | 6-8 | 5-7 |
Daily urine production (ml) | 12.75 ± 1.36 | 9.35 ± 0.81 | 10.18 ± 0.77 | 10.30 ± 0.10 | 11.70 ± 1.84 |
Creatinine (µmol/ml) | 0.92 ± 0.13 | 1.93 ± 0.14 | 4.03 ± 0.53 | 1.37 ± 0.14 | 4.89 ± 0.48 |
Creatinine (µmol/day) | 11.51 ± 1.96 | 18.12 ± 1.97 | 40.37 ± 4.53 | 14.21 ± 1.42 | 48.15 ± 4.00 |
Urea (mol/l) | 85.0 ± 13.8 | 117.1 ± 9.6 | 118.5 ± 8.8 | 109.1 ± 20.1 | 106.6 ± 31.4 |
Urea (mol/day) | 1.07 ± 0.22 | 1.11 ± 0.19 | 1.20 ± 0.09 | 1.12 ± 0.20 | 1.17 ± 0.27 |
After 6 months of pantohematogen administration, alterations in kidney function were observed in some groups, particularly in urine output, creatinine, and urea excretion. Male rats exhibited the most notable changes, with increased urine production and elevated creatinine and urea levels. Two weeks after treatment cessation, specific kidney parameters remained slightly altered compared with the control group. Still, these variations were considered random, unrelated to dosage, and stayed within the normal reference range. In conclusion, the six-month administration of pantohematogen in varying doses (50, 250, and 500 mg/kg) did not cause any harmful effects on kidney function.
To assess the influence of pantohematogen on cardiac function, electrocardiogram (ECG) data were collected from Wistar rats (both male and female) across groups 1, 2, and 3, the control group, and the intact group at three intervals: three months, six months, and 6.5 months (2 weeks after treatment cessation). The rats were anesthetized and positioned supine for ECG recordings, which were obtained using standard leads with an amplification of 1 mV = 20 mm and a speed of 100 mm/s. No significant differences were observed in the ECG readings between the experimental and control groups. Analysis of the P, R, and T wave amplitudes (mV), as well as the P-Q, Q-T, and R-R interval durations (mm), showed no significant deviations (Table 4).
Table 4. The electrical activity of the heart (Х ± m)
Parameters | Doses (mg/kg) | ||||
ECG | Intact | Control | 50 | 250 | 500 |
At 3 months | |||||
P-Q (s) | 0.02 ± 0.00 | 0.03 ± 0.00 | 0.02 ± 0.00 | 0.03 ± 0.00 | 0.03 ± 0.00 |
Q-T (s) | 0.12 ± 0.00 | 0.14 ± 0.01 | 0.11 ± 0.01 | 0.11 ± 0.01 | 0.12 ± 0.01 |
R-R (s) | 0.14 ± 0.01 | 0.16 ± 0.01 | 0.14 ± 0.01 | 0.14 ± 0.01 | 0.15 ± 0.01 |
P (mV) | 0.09 ± 0.02 | 0.06 ± 0.01 | 0.05 ± 0.01 | 0.07 ± 0.02 | 0.04 ± 0.01 |
R (mV) | 0.59 ± 0.07 | 0.48 ± 0.04 | 0.52 ± 0.08 | 0.40 ± 0.07 | 0.57 ± 0.09 |
T (m) | 0.23 ± 0.03 | 0.22 ± 0.03 | 0.14 ± 0.03 | 0.15 ± 0.01 | 0.12 ± 0.03 |
At 6 months | |||||
P-Q (s) | 0.02 ± 0.00 |
| 0.02 ± 0.00 | 0.02 ± 0.00 | 0.02 ± 0.00 |
Q-T (s) | 0.12 ± 0.00 |
| 0.10 ± 0.00 | 0.12 ± 0.01 | 0.11 ± 0.01 |
R-R (s) | 0.14 ± 0.01 |
| 0.12 ± 0.00 | 0.13 ± 0.01 | 0.13 ± 0.01 |
P (mV) | 0.06 ± 0.01 |
| 0.05 ± 0.01 | 0.04 ± 0.01 | 0.08 ± 0.01 |
R (mV) | 0.53 ± 0.04 |
| 0.56 ± 0.08 | 0.49 ± 0.06 | 0.59 ± 0.08 |
T (m) | 0.21 ± 0.04 |
| 0.17 ± 0.04 | 0.14 ± 0.02 | 0.17 ± 0.02 |
At 6.5 months | |||||
P-Q (s) | 0.02 ± 0.00 |
| 0.02 ± 0.00 | 0.02 ± 0.00 | 0.02 ± 0.00 |
Q-T (s) | 0.11 ± 0.00 |
| 0.12 ± 0.00 | 0.11 ± 0.00 | 0.12 ± 0.01 |
R-R (s) | 0.13 ± 0.00 |
| 0.14 ± 0.00 | 0.13 ± 0.01 | 0.14 ± 0.01 |
P (mV) | 0.07 ± 0.01 |
| 0.06 ± 0.01 | 0.05 ± 0.01 | 0.05 ± 0.01 |
R (mV) | 0.46 ± 0.05 |
| 0.66 ± 0.02 | 0.53 ± 0.09 | 0.53 ± 0.09 |
T (m) | 0.15 ± 0.02 |
| 0.21 ± 0.04 | 0.19 ± 0.03 | 0.18 ± 0.03 |
No abnormalities in rhythm or conduction were observed in the rats’ electrocardiographic readings. The experimental groups displayed ECG wave amplitudes and interval durations similar to those of the control and intact groups. While some variations in the ECG parameters were seen in group 2 at the three-month point, these differences had disappeared by the six-month observation.
After treatment ended, a significant increase in R-wave amplitude was observed in group 1 rats (who received 50 mg/kg of pantohematogen) compared with the control group; however, their readings were in alignment with those of the intact rats.
Thus, treatment with pantohematogen at doses of 50, 250, and 500 mg/kg does not affect the electrical activity of the heart.
To investigate the long-term toxicity of pantohematogen, Wistar rats (250-300g) were administered intragastrically at doses of 50, 250, and 500 mg/kg, 7 days per week for 6 months. 30 rats per experimental group were used (15 males and 15 females). The control group included 20 rats (10 males and 10 females) treated with a placebo solution, while another 20 rats (10 males and 10 females) remained untreated (intact).
At three months, 6 rats from each group (3 males and 3 females) were euthanized for analysis, and at six months, 10 rats from each group (5 males and 5 females) were euthanized. Two weeks after the conclusion of the administration period, the remaining rats were euthanized for further examination.
The body weight of rats in the control and intact groups remained comparable throughout the study. However, male rats in group 3 (500 mg/kg pantohematogen) exhibited significantly greater body weight at both the three- and six-month time points compared with the control group.
Upon performing macroscopic inspections of the organs during necropsy, no significant abnormalities were noted in the organs of the experimental rats. Following dissection, parenchymal organs were isolated and weighed, revealing no significant differences in organ weight between the control and intact groups throughout the study. However, in group 3 (500 mg/kg pantohematogen), a reduction in testicular weight was observed at the six-month mark. In contrast, some other internal organs showed increased weight compared with the control. Despite this, the organ weight ratios were largely consistent with the control group, except for the thymus (observed in the 250 and 500 mg/kg groups at three months), liver (500 mg/kg at six months), and testicles (all doses at six months and 250 and 500 mg/kg at 6.5 months).
At both the six-month and six-and-a-half-month intervals, microscopic evaluations were carried out on tissues from the brain, pituitary gland, heart, lung, liver, kidney, stomach, intestines (small and large), pancreas, thyroid glands, spleen, thymus, adrenal glands, ovaries, uterus, and testicles. Tissues were prepared using formalin fixation and paraffin embedding, followed by hematoxylin and eosin staining.
Histopathological assessments of the experimental rats’ organs showed no significant changes compared to control and intact rats. The brain appeared unaffected, with no signs of hyperemia or infiltration in the pia mater. The cortex and basal ganglia showed normal cellularity, and glial cell counts were within expected ranges. Similarly, no signs of myocardial damage were observed in the heart, where the cardiomyocytes were of typical size, and the transverse striations were intact. The lung tissue was free of obstruction, with no thickening in the interalveolar septa or dilation of the airways and alveoli. The thymus exhibited normal cellularity and was divided into two lobes.
The liver appeared unaffected, with no hyperemia and preserved lobular architecture. Hepatocytes exhibited normal features. There was occasional focal lymphocytic and macrophage infiltration around the portal tracts. The gastric mucosa was structurally normal, with no signs of edema or hyperemia. Gastric glands remained undilated, and secretory cells were of typical size and shape.
Examinations of the small and large intestines revealed no pathological changes. The epithelial lining of the small intestine, particularly in the crypts and villi, showed normal structure and cell division rates. The pancreas was unremarkable, with no evidence of edema, and the acinar cells had typical organization.
Kidney examinations indicated minor venous congestion in the tissue, but the glomerular structure and cellularity were normal. In male rats, the renal tubular epithelium was normal. Female rats in all groups exhibited focal deposits of calcium salts in the renal tubular epithelium, without a significant inflammatory reaction. The adrenal cortex was structurally intact, but the medullary area showed slight congestion, with occasional macrophages, megakaryocytes, lymphocytes, and siderophages.
No signs of edema or infiltration were detected in the testicular tissues. While the spermatogenic epithelium remained intact, a decrease in the number of seminiferous tubular cells was observed, unrelated to dosage. Leydig cells remained intact, and the number of meiotic stages per 100 seminiferous tubules remained within expected limits.
Examinations of the ovaries revealed no hemodynamic changes, with follicles and corpus luteum at various stages of development. The endometrial glands were mildly tortuous, with no significant desquamation, and leukocytes infiltrated the connective tissue between the glands. The myometrium showed mild congestion.
Both the experimental and control rats exhibited slight enlargement of the thyroid glands. The gland tissue showed mild plethoric changes, and the connective tissue between lobules was thickened. A moderate degree of lymphoid infiltration was seen, resembling diffuse parenchymal goiter in some rats. Additionally, some rats displayed mild hyperemia in the anterior pituitary gland.
The administration of pantohematogen at the doses of 155, 775, and 1550 mg/kg (equivalent to 50, 250, and 500 mg/kg) did not show any significant effects on the overall health, peripheral blood parameters, or the functionality of the bone marrow, liver, kidneys, or heart.
Nevertheless, the 500 mg/kg dose resulted in some noticeable outcomes: (a) an increase in weight gain in male rats, (b) heightened emotional responses at 3 months in both male and female rats, and (c) greater locomotor activity in female rats.
The morphological assessments indicated that at doses of 250 and 500 mg/kg, there was an increase in liver weight and a reduction in testicular size in male rats, with the effects still evident 2 weeks after treatment ended.
Upon conducting histological analysis, no abnormalities were observed in the organs of the experimental animals when compared with the control or intact groups.
The administered doses were considerably higher than the typical human dose, ranging from 2 to 20 times the usual human dose per kilogram of body weight. The study concluded that pantohematogen was not toxic at the given doses.
The authors would like to thank the administration of the “South” company for providing the opportunity to conduct this research.
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