دراسة تأثير السيراتوبيبتيدازون-أسيتيل سيستين ضد الأضرار الناجمة عن الميثوتريكسات في خصيتي ذكور الفئران

Investigating the Effects of Serratiopeptidase and N-acetyl cysteine against Methotrexate - induced damages in Male Rats testes

Summary
The study explored the Effects of Methotrexate induced damages on the male reproductive system of rats and the potential protective role of Serratiopeptidase and N-acetyl cysteine . Thirty-five adult male albino rats were divided into five groups : Negative control group: Received normal saline daily for 56 day, Methotrexate group: Received Methotrexate 5 mg/kg body weight, daily by intraperitoneal injection for 56 day. N-Acetylcysteine group : Received Methotrexate 5 mg/kg body weight, daily by intraperitoneal injection and N-Acetylcysteine 600mg/kg body weight orally , daily for 56 day. Serratiopeptidase group : : Received Methotrexate 5 mg/kg body weight, daily by intraperitoneal injection Serratiopeptidase 5mg/kg body weight orally , daily for 56 day. NAC+SER group: Received Methotrexate 5 mg/kg body weight, daily by intraperitoneal injection and N-Acetylcysteine 600mg/kg body weight orally , daily for 56 day + Serratiopeptidase 5mg/kg body weight orally , daily for 56 day. Rats were given a chloroform anesthetic to make them unconscious, and then blood samples were taken from the heart `to examine Oxidative stress biomarkers include the reduced glutathione(GSH), Malondialdehyde (MDA) and total antioxidant capacity (TAOC) , The reproductive hormone levels :Testosterone , follicle-stimulating hormone (FSH) and luteinizing hormone (LH) . and dissected animals to get the Testicular and epididymis tissues for histological investigation and sperm analysis and of Nuclear factor erythroid 2-related factor 2 (Nrf2). The results of experimental Shaw the Methotrexate toxicity significantly disrupted testicular function, causing a marked decline in testosterone and LH while increase in FSH levels. It also led to elevated levels of oxidative stress markers such as malondialdehyde (MDA), while the essential antioxidant enzymes including SOD show increase and decrease in glutathione (GSH) , also Sperm count, motility, morphology, and viability were all significantly impaired Histologically, MTX induced extensive damage in testicular tissue including necrosis, vascular congestion, and architectural disintegration of seminiferous tubules. The Efficacy of N-acetylcysteine and Serratiopeptidase treatment markedly improved hormonal profiles and antioxidant levels. Its function as a precursor to glutathione, N-acetylcysteine improve the sperm viability, motility, and histological structure by scavenging reactive oxygen species and enhancing cellular antioxidant capacity. And the Synergistic Effect of N-acetylcysteine with Serratiopeptidase demonstrated a synergistic protective effect, outperforming each agent used alone. It led to significant normalization of hormonal levels, enhancement of antioxidant defense (including GSH and TAOC), and maintenance of normal testicular tissue.
Conclusions: The results provide strong evidence that NAC, especially when combined with SER, offers substantial protection against such damage, making this combination a promising approach for mitigating chemotherapy-related reproductive toxicity.