Molecular insights into the antioxidative and anti-inflammatory effects of P-coumaric acid against bisphenol A-induced testicular injury: In vivo and in silico studies.

This study investigated the protective effects of p-coumaric acid (PCA) against bisphenol A (BPA)-induced testicular toxicity in male rats. The rats were divided into control, BPA, BPA+PCA50, BPA+PCA100, and PCA100 groups. Following a 14-day treatment period, various analyses were conducted on epididymal sperm quality and testicular tissues. PCA exhibited dose-dependent cytoprotective, antioxidant, and anti-inflammatory effects, ameliorating the decline in sperm quality induced by BPA. The treatment elevated antioxidant enzyme activities (SOD, GPx, CAT) and restored redox homeostasis by increasing cellular glutathione (GSH) and reducing malondialdehyde (MDA) levels. PCA also mitigated BPA-induced proinflammatory responses while reinstating anti-inflammatory IL-10 levels. Apoptotic parameters (p53 and p38-MAPK) were normalized by PCA in BPA-treated testicular tissue. Immunohistochemical and immunofluorescent analyses confirmed the cytoprotective and anti-inflammatory effects of PCA, evidenced by the upregulation of HO-1, Bcl-2, and Nrf-2 and the downregulation of the proapoptotic gene Bax in BPA-induced testicular intoxication. PCA corrected the disturbance in male reproductive hormone levels and reinstated testosterone biosynthetic capacity after BPA-induced testicular insult. In silico analyses suggested PCA's potential modulation of the oxidative stress KEAP1/NRF2/ARE pathway, affirming BPA's inhibitory impact on P450scc. This study elucidates BPA's molecular disruption of testosterone biosynthesis and highlights PCA's therapeutic potential in mitigating BPA's adverse effects on testicular function, showcasing its cytoprotective, anti-inflammatory, and hormone-regulating properties. The integrated in vivo and in silico approach offers a comprehensive understanding of complex mechanisms, paving the way for future research in reproductive health and toxicology, and underscores the importance of employing BPA-free plastic wares in semen handling.

Selenium reduces acrylamide-induced testicular toxicity in rats by regulating HSD17B1, StAR, and CYP17A1 expression, oxidative stress, inflammation, apoptosis, autophagy, and DNA damage.

This study investigated the effects of Selenium (Se) on testis toxicity induced by Acrylamide (ACR) in rats. In our study, 50 male adult rats were used, and the rats were divided into five groups; control, ACR, Se0.5 + ACR, Se1 + ACR, and Se1. Se and ACR treatments were applied for 10 days. On the 11th day of the experimental study, intracardiac blood samples from the rats were taken under anesthesia and euthanized. Sperm motility and morphology were evaluated. Dihydrotestosterone, FSH, and LH levels in sera were analyzed with commercial ELISA kits. MDA, GSH, TNF-α, IL-6, and IL-1ß levels and SOD, GPx, and CAT, activities were measured to detect the level of oxidative stress and inflammation in rat testis tissues. Expression analysis of HSD17B1, StAR, CYP17A1, MAPk14, and P-53 as target mRNA levels were performed with Real Time-PCR System technology for each cDNA sample synthesized from rat testis RNA. Testicular tissues were evaluated by histopathological, immunohistochemical, and immunofluorescent examinations. Serum dihydrotestosterone and FSH levels decreased significantly in the ACR group compared to the control group, while LH levels increased and a high dose of Se prevented these changes caused by ACR. A high dose of Se prevented these changes caused by ACR. ACR-induced testicular oxidative stress, inflammation, apoptosis, changes in the expression of reproductive enzymes, some changes in sperm motility and morphology, DNA, and tissue damage, and Se administration prevented these pathologies caused by ACR. As a result of this study, it was determined that Se prevents oxidative stress, inflammation, apoptosis, autophagy, and DNA damage in testicular toxicity induced by ACR in rats.

Reproductive Effects of S. boulardii on Sub-Chronic Acetamiprid and Imidacloprid Toxicity in Male Rats.

The potential health-promoting effects of probiotics against intoxication by pesticides is a topic of increasing commercial interest with limited scientific evidence. In this study, we aimed to investigate the positive effects of probiotic Saccharomyces boulardii on the male reproductive system under low dose neonicotinoid pesticide exposure conditions. We observed that acetamiprid and imidacloprid caused a degeneration and necrosis of the spermatocytes in the tubular wall, a severe edema of the intertubular region and a hyperemia. This was concomittant to increased levels of 8-hydroxy-2'-deoxyguanosine reflecting oxidative stress, and an increase in caspase 3 expression, reflecting apoptosis. According to our results, Saccharomyces boulardii supplementation mitigates these toxic effects. Further in vivo and clinical studies are needed to clarify the molecular mechanisms of protection. Altogether, our study reinforces the burden of evidence from emerging studies linking the composition of the gut microbiome to the function of the reproductive system.

Effects of naringin on oxidative stress, inflammation, some reproductive parameters, and apoptosis in acrylamide-induced testis toxicity in rat.

Acrylamide (ACR) is used in many fields such as cosmetics, paper, and textile industries. It also occurs at very high temperatures in some foods. Gonadotoxic effects of ACR have been found in experimental animals. Many studies use flavonoids to prevent the reproductive side effects of ACR. Naringin (NA) is a flavonoid and it has been determined by studies that it has no toxic effect on tissues. In our study, we aimed to determine the protective effect of NA against the damage of ACR on testicular tissue and the reproductive system in rats. In our study, 50 Spraque Dawley male rats weighing 220-250 grams were used. Control: Only intragastric saline was administered for 10 days. ACR: Animals received ACR (40 mg/kg, intraperitoneally) for 10 days. NA50+ACR: Animals were given NA for 10 days and each NA was one hour after the administration of ACR. NA100+ACR: Animals received NA for 10 days and one hour after each NA was given ACR. NA100: Animals were given NA for 10 days. At the end of the applications, the rats were euthanized by cervical dislocation under anesthesia. Serum FSH, LH, and Dihydrotestosterone levels were compared between the groups. In addition, oxidative stress, inflammation, expression of some reproductive enzymes, and apoptosis markers were determined in testicular tissues. When these parameters were compared between groups, ACR induced testicular dysfunction and tissue damage in rats. We determined that only the NA application did not cause tissue damage. and the administration of NA along with ACR significantly reduced ACR-induced testis toxicity.

Ameliorative effect of hesperidin on streptozotocin-diabetes mellitus-induced testicular DNA damage and sperm quality degradation in Sprague-Dawley rats.

This study aimed to investigate the effect of hesperidin on reproductive damage caused by diabetes mellitus. A total of 24 adult male rats were divided into four groups: control group, hesperidin group, diabetes mellitus group, and diabetes mellitus + hesperidin group. The study was conducted for 4 weeks. At the end of the study, the rats were sacrificed and testicular oxidative stress markers (MDA, GSH, GSH-Px, SOD, and CAT), DNA damage in testes (8-OHdG), and routine sperm parameters were evaluated. According to the results of the study, most of the parameters were similar in the control and hesperidin groups but CAT activity in the hesperidin group was statistically higher than the control group. Also, diabetes mellitus (DM) significantly increased MDA levels and decreased enzymatic antioxidant (GSH-Px, SOD, CAT) activities and nonenzymatic (GSH) antioxidant levels. On the other hand, hesperidin supplementation significantly decreased oxidative stress and increased enzymatic antioxidant activities and nonenzymatic antioxidant levels due to the antioxidant effect. Also, DM increased DNA damage levels in testicular tissue and hesperidin supplementation significantly decreased DNA damage levels in testes of diabetic male rats. Besides, sperm motility significantly decreased while abnormal sperm rate and dead sperm rate were significantly increased in diabetic rats. Hesperidin supplementation significantly reduced these side effects in diabetic rats. In conclusion, hesperidin supplementation could be beneficial for decreasing the side effects on the male reproductive system caused by DM in rats. PRACTICAL APPLICATIONS: Diabetes is an important metabolic disease, affecting quality of life and fertility. Hesperidin has an antioxidant effect and has a potential protective effect on reproductive toxicity in diabetic male rats. Hesperidin decreased oxidative stress, and DNA damage in testis resulted from hyperglycemia and improved sperm quality in diabetic rats. The hesperidin supplementation could be a good strategy to protect male fertility in diabetic patients.

Chrysin protects against testicular toxicity caused by lead acetate in rats with its antioxidant, anti-inflammatory, and antiapoptotic properties.

In the present study, the protective effects of chrysin (CHR) against testicular damage caused by lead acetate (PbAc) were examined. In this way, 30 min after rats were given 25 and 50 mg/kg/b.w CHR orally for seven consecutive days, 30 mg/kg/b.w PbAc was administered orally. In biochemical analysis of testicular tissue, it was found that PbAc-reduced antioxidant parameters [glutathione peroxidase (GPx), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT)], while it increased lipid peroxidation, inflammatory markers [nuclear factor kappa-B (NF-κB), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE-2), and inducible nitric oxide synthase (iNOS)], and 8-hydroxy-2'-deoxyguanosine (8-OHdG). In the immunohistochemical examination, it was determined that PbAc increased the expression of tumor necrosis factor-α (TNF-α) and caspase-3. Accordingly, PbAc was found to cause a decrease in sperm motility and an increase in the percentage of dead sperm. However, it has been observed that CHR relieves oxidative stress due to its antioxidant properties, thus protecting against inflammation and apoptosis. It also allowed the CHR sperm parameters to return to control group levels. The results revealed that CHR could be a natural substance to be used in Pb-induced testicular toxicity. PRACTICAL APPLICATIONS: Lead (Pb) is an important environmental contaminant heavy metal. Pb is believed to reduce fertility in men. Oxidative stress plays a significant role in the damage caused by Pb to testicular tissue. CHR is an antioxidant substance that occurs naturally in various plants and has various pharmacological properties. In the present study, it was investigated whether CHR has a protective effect against testicular toxicity induced by PbAc. The results revealed that in rats, CHR protects the testicular tissue from PbAc toxicity by showing antioxidant, anti-inflammatory and anti-apoptotic effects, thus bringing sperm parameters closer to normal.

The effects of hesperidin on colistin-induced reproductive damage, autophagy, and apoptosis by reducing oxidative stress.

This study has been conducted to investigate the effect of hesperidin on colistin-induced reproductive damage in male rats. Twenty-four adult male Sprague Dawley rats were used as animal material. They were divided into four groups: control group, received physiological saline for 7 days by oral gavage; hesperidin group, received 300 mg/kg day hesperidin for 7 days; colistin group, received 73 mg/kg (total dose) colistin during 7 days; and colistin + hesperidin group, received 300 mg/kg day hesperidin following the colistin treatment. At the end of the study, routine spermatological parameters and biochemical evaluations were assayed. Also, apoptosis and autophagy biomarkers in testes were evaluated. Colistin increased oxidative stress, apoptosis and autophagy expression levels in testis. Hesperidin supplementation significantly decreased the oxidative stress levels in the testes of the colistin + hesperidin group when compared to the colistin group. The highest apoptosis and autophagy expression levels were detected in the colistin group. These values were statistically lower in the colistin + hesperidin group when compared to the colistin group. Colistin treatment decreased the percentage of sperm motility and increased sperm abnormality. Hesperidin supplementation mitigated significantly mentioned side effects compared to the colistin group. In conclusion, hesperidin supplementation can be a good strategy to mitigate colistin-induced testicular toxicity.

Protective effect of rutin on mercuric chloride-induced reproductive damage in male rats.

This study investigated the effects of rutin against reproductive damage caused by toxic mercury in male rats. Thirty-five Sprague Dawley rats were used. Control group was injected with saline for 7 days. The rutin-100 group received 100 mg/kg/b.w. rutin for 7 days. Mercuric chloride (HgCl2 ) group received 1.23 mg/kg/b.w. of HgCl2 for 7 days. Mercury chloride + rutin-50 group received 50 mg/kg/b.w. rutin and HgCl2 1.23 mg/kg/b.w. for 7 days. HgCl2  + rutin-100 group received 100 mg/kg/b.w. rutin and HgCl2 1.23 mg/kg/b.w. for 7 days. It was detected that HgCl2 treatment increased malondialdehyde (MDA) levels, tumour necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) expressions, necrosis and degeneration of spermatogonium, dead and abnormal sperm percentages; tubular walls thinning; and decreased antioxidant enzyme activities and sperm motility. It was determined that rutin application reduced testicular damage caused by HgCl2 . In conclusion, rutin administration may treat HgCl2 toxicity in testes.

Palliative effect of curcumin on doxorubicin-induced testicular damage in male rats.

This study aimed to investigate the effect of curcumin (CUR) on doxorubicin (DOX)-induced testicular damage in male rats. Thirty-five adult male Wistar rats were used. Control group was received saline for 7 days. CUR group received CUR for 7 days. DOX group received single dose DOX on the 5th day. DOX+ CUR-100 group received 100 mg/kg/day CUR for 7 days and DOX injection on the 5th day. DOX + CUR-200 group received 200 mg/kg/day CUR for 7 days and DOX injection on the 5th day. DOX treatment decreased in sperm motility rate, live sperm percentages, cellular antioxidants, and increased malondialdehyde (MDA) levels, necrosis, degenerations, and slimming in seminiferous tubules, and DNA damages in testes by inducing oxidative stress. CUR treatment mitigated significantly these side effects when compared with DOX group in a dose-dependent manner. In conclusion, CUR treatment can be used in the mitigation of DOX-induced testicular toxicity.

Improvement in colistin-induced reproductive damage, apoptosis, and autophagy in testes via reducing oxidative stress by chrysin.

This study aimed to investigate the effect of chrysin on colistin-induced reproductive toxicity. Twenty-eight adult male Sprague-Dawley rats were divided into four groups of seven rats each. Group I received physiological saline for 7 days. Group II received 50 mg/kg/day chrysin for 7 days. Group III received a total dose of 73 mg/kg colistin for 7 days. Group IV received 50 mg/kg/day chrysin by an oral gavage after the colistin treatment. Colistin causes an increase in oxidative stress (OS) in the testis. Chrysin treatment significantly decreased the OS in the chrysin + colistin group compared with the colistin group. The highest caspase-3 and LC3B expression levels were found in the colistin group and these levels were statistically lower in the chrysin + colistin group. Colistin treatment caused a decrease in sperm motility and an increase in sperm abnormality. Chrysin treatment mitigated these side effects significantly. In conclusion, chrysin treatment can be beneficial against colistin-induced reproductive toxicity.

Ameliorative Effect of Carvacrol on Cisplatin-Induced Reproductive Damage in Male Rats.

Cisplatin (CP) treatment causes the damage in male reproductive system. Carvacrol (CARV) is an antioxidant that is naturally found in some plants. We aimed to investigate the effect of CARV on CP-induced reproductive toxicity in male rats. Eighteen adult male Sprague-Dawley rats were used. The control group (n = 6) was treated orally with physiological saline (PS) daily for 14 days and a single intraperitoneal (IP) PS injection on day 10. The CP group (n = 6) was administered with daily oral PS for 14 days and a single IP injection of 10 mg/kg CP on day 10. The CARV + CP group (n = 6) was treated with daily 75 mg/kg oral CARV for 14 days and a single IP injection of 10 mg/kg CP on day 10. CP treatment caused the damage on some spermatological parameters (motility, live sperm rate, and abnormal sperm rate), increased the oxidative stress, and induced testicular degeneration and apoptosis. However, CARV treatment mitigates CP-induced reproductive toxicity.

Effects of pomegranate juice consumption on sperm quality, spermatogenic cell density, antioxidant activity and testosterone level in male rats.

BACKGROUND & AIM: Pomegranate fruit is inescapably linked with fertility, birth and eternal life because of its many seeds. The aim of this study was to investigate the effects of pomegranate juice (PJ) consumption on sperm quality, spermatogenic cell density, antioxidant activity and testosterone level of male healthy rats. METHODS: Twenty-eight healthy adult male Wistar rats were divided into four groups; each group containing seven rats. One milliliter distilled water, 0.25 mL PJ plus 0.75 mL distilled water, 0.50 mL PJ plus 0.50 mL distilled water and 1 mL PJ were given daily for seven weeks by gavage to rats in the first, second, third and fourth groups, respectively. Body and reproductive organ weights, spermatogenic cell density, sperm characteristics, levels of antioxidant vitamins, testosterone, and lipid peroxidation and, antioxidant enzyme activities were investigated. All analyses were done only once at the end of the seven week study period. Data were compared by analysis of variance (ANOVA) and the degree of significance was set at P<0.05. RESULTS: A significant decrease in malondialdehyde (MDA) level and marked increases in glutathione (GSH), glutathione peroxidase (GSH-Px) and catalase (CAT) activities, and vitamin C level were observed in rats treated with different doses of PJ. PJ consumption provided an increase in epididymal sperm concentration, sperm motility, spermatogenic cell density and diameter of seminiferous tubules and germinal cell layer thickness, and it decreased abnormal sperm rate when compared to the control group. CONCLUSION: The results suggest that PJ consumption improves sperm quality and antioxidant activity of rats.