Mechanistic insight into the protective effects of fisetin against arsenic-induced reproductive toxicity in male rats

Arsenic is one of the most hazardous environmental contaminants, which adversely affects the dynamics of male reproductive system. Fisetin (FIS) is a bioactive flavonoid, which is known to exert strong antioxidative effects. Therefore, the current research was planned to evaluate the alleviative efficacy of FIS against arsenic-induced reproductive damages. Forty-eight male albino rats were divided into 4 groups (n = 12), which were treated as follows: (1) Control, (2) Arsenic-intoxicated group (8 mg kg-1), (3) Arsenic + FIS-treated group (8 mg kg-1 + 10 mg kg-1), and (4) FIS-treated group (10 mgkg-1). After 56 days of treatment, the biochemical, lipidemic, steroidogenic, hormonal, spermatological, apoptotic and histoarchitectural profiles of rats were analyzed. Arsenic intoxication reduced the enzymatic activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GSR), in addition to glutathione (GSH) level. Conversely, the levels of thiobarbituric acid reactive substance (TBARS) and reactive oxygen species (ROS) were increased. Moreover, it escalated the level of low-density lipoprotein (LDL), triglycerides and total cholesterol, while declining the level of high-density lipoprotein (HDL). Furthermore, steroidogenic enzymes expressions, 3β-hydroxysteroid dehydrogenase (HSD), 17β-HSD, steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (CYP11A1) and 17α-hydroxylase/17, 20-lyase (CYP17A1), were found to be reduced, which brought down the level of testosterone. Besides, the levels of gonadotropins (LH and FSH) were decreased. Additionally, a decline in sperm mitochondrial membrane potential (MMP), motility, epididymal sperm count and hypo-osmotic swelling (HOS) coil-tailed sperms was observed, whereas the dead sperms and structural damages (head, midpiece and tail) of sperms were escalated. Moreover, arsenic exposure up-regulated the mRNA expressions of apoptotic markers, namely Bax and caspase-3, whereas lowered the expression of anti-apoptotic marker, Bcl-2. In addition, it induced histoarchitectural changes in testes of rats. However, FIS treatment resulted in remarkable improvements in testicular and sperm parameters. Therefore, it was inferred that FIS could serve as a therapeutic candidate against arsenic-generated male reproductive toxicity attributing to its anti-oxidant, anti-lipoperoxidative, anti-apoptotic, and androgenic efficacy.

 

Comments：

The current research aimed to investigate the effectiveness of fisetin (FIS), a bioactive flavonoid known for its strong antioxidant effects, in mitigating the reproductive damage caused by arsenic exposure in male albino rats. The study involved four groups of rats, including a control group, an arsenic-intoxicated group, an arsenic + FIS-treated group, and a FIS-treated group. After 56 days of treatment, the researchers analyzed the rats' biochemical, lipidemic, steroidogenic, hormonal, spermatological, apoptotic, and histoarchitectural profiles.

The findings revealed that arsenic exposure reduced the activities of enzymatic antioxidants, including catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GSR), as well as glutathione (GSH) levels. Conversely, the levels of thiobarbituric acid reactive substance (TBARS) and reactive oxygen species (ROS) were increased. Arsenic exposure also increased the levels of low-density lipoprotein (LDL), triglycerides, and total cholesterol, while decreasing the level of high-density lipoprotein (HDL). Additionally, steroidogenic enzymes expressions and testosterone levels were reduced, while the levels of gonadotropins (LH and FSH) were decreased.

Furthermore, arsenic exposure led to a decline in sperm mitochondrial membrane potential (MMP), motility, epididymal sperm count, and hypo-osmotic swelling (HOS) coil-tailed sperms, while increasing the dead sperms and structural damages of sperms. Arsenic exposure also upregulated the mRNA expressions of apoptotic markers, including Bax and caspase-3, while lowering the expression of anti-apoptotic marker, Bcl-2. Additionally, arsenic exposure caused histoarchitectural changes in the testes of rats.

However, FIS treatment resulted in significant improvements in testicular and sperm parameters. FIS was found to have anti-oxidant, anti-lipoperoxidative, anti-apoptotic, and androgenic efficacy, making it a potential therapeutic candidate against arsenic-generated male reproductive toxicity.

In conclusion, the study suggests that FIS can effectively alleviate arsenic-induced reproductive damage in male albino rats, indicating its potential for use in treating arsenic-induced male reproductive toxicity in humans.