Thyroid and reproductive hormones disruption as well as kallikrein-3 level in dimethyl nitrosamine-induced toxicity: Effects of ascorbate treatment in male wistar rats

Abstract

Information on dimethyl nitrosamine (DMN)-induced toxicity on endocrine functions is still scanty. This study therefore investigated the outcomes of DMN-induced toxicity on endocrine (thyroid and reproductive) functions, as well as kallikrein-3 level, and effects of ascorbate treatments in male wistar rats. Thirty animals divided into six groups of five rats each were used. Group I animals were the normal control, group II animals served as vehicle control and were administered a single intraperitoneal dose of normal saline, groups III and IV were intraperitoneally injected with a single dose of 30 mg/kg DMN for 48 h, but group IV animals were post-treated orally with 5.71 mg/kg body weight (400 mg/70 kg) ascorbate for seven days, group V animals were pre-treated with same dose of ascorbate orally for seven days before intraperitoneal injection of DMN, while group VI animals were orally administered ascorbate only for seven days. Compared with control, DMN administration resulted in significant decrease (p < 0.05) in serum total cholesterol, testosterone (TST), luteinizing hormone (LH), free triiodothyronine (fT₃), and kallikrein III (KLK-3) levels, as well as non-significant increase in serum thyroid stimulating hormone (TSH) level. Pre-treatment with ascorbate significantly increase LH and KLK-3 levels, while post-treatment significantly increase fT₃ level. Also, pre-treatment with ascorbate significantly reduced TSH level, while there was no significant difference in TST level following ascorbate treatments. From our findings and to some extent, ascorbate demonstrates ameliorative effects against DMN-induced hormonal disruption in male wistar rats, and this may be attributed to its antioxidant property.

Keywords: Ascorbate; Dimethyl nitrosamine; Kallikrein-3; Reproductive hormone; Thyroid hormone.

Fig. 1

Effects of pre- and post-ascorbate treatments on total cholesterol levels in DMN- induced toxicity. Values are expressed as mean ± SEM (n = 5). Bars with different letters are significantly different (p < 0.05), while bars with similar letters are not significant (p > 0.05). DMN = dimethyl nitrosamine; ASCB = ascorbate.

Fig. 2

Effects of pre- and post-ascorbate treatments on LH levels in DMN- induced toxicity. Values are expressed as mean ± SEM (n = 5). Bars with different letters are significantly different (p < 0.05), while bars with similar letters are not significant (p > 0.05). DMN = dimethyl nitrosamine; ASCB = ascorbate.

Fig. 3

Effects of pre- and post-ascorbate treatments on TST levels in DMN- induced toxicity. Values are expressed as mean ± SEM (n = 5). Bars with different letters are significantly different (p < 0.05), while bars with similar letters are not significant (p > 0.05). DMN = dimethyl nitrosamine; ASCB = ascorbate.

Fig. 4

Effects of pre- and post-ascorbate treatments on TSH levels in DMN- induced toxicity. Values are expressed as mean ± SEM (n = 5). Bars with different letters are significantly different (p < 0.05), while bars with similar letters are not significant (p > 0.05). DMN = dimethyl nitrosamine; ASCB = ascorbate.

Fig. 5

Effects of pre- and post-ascorbate treatments on fT3 levels in DMN- induced toxicity. Values are expressed as mean ± SEM (n = 5). Bars with different letters are significantly different (p < 0.05), while bars with similar letters are not significant (p > 0.05). DMN = dimethyl nitrosamine; ASCB = ascorbate.

Fig. 6

Effects of pre- and post-ascorbate treatments on KLK-3 levels in DMN- induced toxicity. Values are expressed as mean ± SEM (n = 5). Bars with different letters are significantly different (p < 0.05), while bars with similar letters are not significant (p > 0.05). DMN = dimethyl nitrosamine; ASCB = ascorbate.