The Impact of Cholecalciferol on the Sex Hormones Level and Serum Biochemical Indices in Rat Males With Experimental Gonadopathy

Abstract

The testicular deficiency, cryptorchidism, varicocele, endocrine pathologies are the main causes of men infertility. The internal diseases of testicles lead to fertility declining in the major part of cases which explains the importance of studying of gonadopathies᾿ methods of correction. In recent times, vitamin D is noted among remedies suitable for effective correction of reproductive system. The aim of investigation: to determine the sex hormones levels and biochemical indices in serum of rats’ males with experimental testicles damage under the condition of vitamin D3 correction used separately or in combination with Tribestan®. Materials and methods. The experiment has been carried out on mature Vistar rats’ males; group of animals: S-model (animals with serotonin-induced gonads damage, gonadopathy (GP)); S+solvent (rats with gonadopathy which received solvent); S+vit. D3 (animals with gonadopathy received vitamin D3); S+Tr (rats with gonadopathy obtained Tribestan (Tr) – reference medicine); S+vit. D3+Tr (animals received both remedies); control – intact males. The activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), general content of nitrogen oxide cycle metabolites (NОх), concentration of TBARS and sex hormones Ts and E2 have been determined; their ratio has been calculated. Results. The NOх was increased in S-model rats. The application of vit. D3 or Tr has caused decreasing of NOх concentration in comparison with S-model group. The complex using of vit. D3 and Tr has had positive effect as for protection against oxidative stress (OS). The concentration of NOx in rats of S+vit. D3+Tr was by 56% less than in S-model group, but, as in the other experimental groups of animals, has remained increased relative to control group. The deficiency of free arginine in blood serum has been detected in all experimental groups comparing with Control group. The application of vit. D3 hasn’t affected on the arginine content. Tr has positively influenced the arginine level: the increasing of concentration of this amino acid was 95% relative to S-model group, but was less by 48% than values of intact animals. After application of Tr and vit. D3 together the concentration of arginine was higher by 2.2 times than in rats of S-model group, but hasn’t reached the values of intact animals. The concentration of TBARS has increased under the condition of GP. The using of vit. D3 has led to reducing, but not to normalizing of TBARS content. The concentration of TBARS in rats of S+Tr group was by 1.9 times lower than in rats with GP and by two times higher than in intact animals. Simultaneous using of Tr and vit. D3 has been effective as for reducing of lipid peroxidation (LP) intensity. The concentration of TBARS in S+vit. D3+Tr group has declined by 2.2 times comparing with values of animals with GP. The combination of Tr and vitamin D3 was more effective than cholecalciferol single using as for protection against OS and LP reducing and has demonstrated activity at the level of reference drug. GP has led to increasing of ALT activity 2.4 times and AST – by 2 times comparing with control group. The application of Tr, vit. D3 or their complex hasn’t changed ALT activity which was statistically higher than intact animals’ values. The activity of AST was increased in animals with GP and reduced after experimental correction of GP consequences. Vitamin D3 monotherapy has reduced by 32% the activity of AST comparing with animals with GP. AST concentration in males’ blood serum was decreased too with the combined use of Tr and vitamin D3 comparing with untreated animals. Thus, vitamin D has positively impacted the AST level in combined use with Tr as well as monotherapy. Serotonin-induced experimental GP has caused the declining of general Ts concentration in blood serum of animals of all experimental groups. The application of vitamin D3 hasn’t demonstrated androgen correcting activity. Tr has positively influenced androgen synthesized function: Ts concentration has increased by 95% comparing with S-model group, but remained lower by 31% than in intact animals. The Ts concentration in S+vit. D3+Tr group was 2.1 times higher than in animals with GP. However, Ts values in this group haven’t reached Control group values and were by 25% less. The concentration of estradiol in all experimental groups has corresponded to the values of intact animals. The calculation of Ts/Е2 ratio has shown to be decreased in S-model, S+solvent, S+vit. D3 groups in comparison with intact animals. The Ts/Е2 ratio has normalized in groups with GP treated by reference drug separately or in combination with vitamin D3. Conclusions: The application of cholecalciferol has considerably decreased NOx and TBARS concentrations, but hasn’t affected on arginine level which has declined with the gonadopathy. Vitamin D has caused reducing of aspartate aminotransferase activity in serum and hasn’t had androgenic and estrogenic effects. The application of Tribestan has led to the pro-oxidative/antioxidative balance recovery under the condition of experimental gonadopathy. This medicine has reduced the high level of aspartate aminotransferase activity, increased testosterone level and normalized testosterone/estradiol ratio in blood serum of experimental animals. The application of vitamin D and Tribestan in combination has led to improvement of androgenic status and has demonstrated better effect as for protection against oxidative stress and lipid peroxidation than cholecalciferol as a monotherapy.

Morphological structure of testicles under conditions of experimental gonadopathy and after the administration of cholecalciferol in comprehensive correction schemes

“…The obtained results are supported by the literature data on the histological structure of the testes and the submicroscopic architecture of Sertoli cells after the use of Serotonin hydrochloride [6,26]. Under the influence of Serotonin hydrochloride, the number of activated hormone-producing Leydig cells decreases, as observed in our study and reported in the literature, which leads to a decrease in the androgen status of the animals' bodies, and is confirmed not only indirectly by the test of crystallization of the prostate gland secretion (see Table 3) but also by a decrease in the level of male sex hormone associated with experimental gonadopathy [4].…”

“…Notes: 1 -Statistically significant differences compared to the control group, p<0.05; 2 -statistically significant differences compared to the S group, p<0.05; 3 -statistically significant differences compared to the S+vit. D 3 group, p<0.05; 4 -statistically significant differences compared to the S+Tr group, p<0.05.…”

“…Sertoli cells were observed in the tubular wall (often with destructive changes, most of which appeared swollen, the Notes: 1 -statistically significant differences compared to the data of the control group, p<0.05; 2 -statistically significant differences compared to the data of the S group, p<0.05; 3 -statistically significant differences compared to the data of the S+vit. D 3 group, p<0.05; 4 -statistically significant differences compared to the data of the S+Tr group, p<0.05. nuclei sharply displaced or absent altogether, the regular arrangement of these cells was disrupted, with either individual cells or clusters present) and irregularly distributed undifferentiated cells of varying number. Some tubules were filled with necrotic debris.…”

“…The testes of intact rats served as a general control in our studies on the effects of vitamin D 3 (Fig. 1) [4], administered both independently and in various correction schemes for experimental reproductive disorders, their morphological structure and morphometric indicators corresponded to normal values (Table 2).…”