The deleterious effects of sofosbuvir and ribavirin (antiviral drugs against hepatitis C virus) on different body systems in male albino rats regarding reproductive, hematological, biochemical, hepatic, and renal profiles and histopathological changes.

Sofosbuvir is one of the crucial drugs used in the treatment of chronic hepatitis C virus (HCV) in adults and children with compensated liver disease, including cirrhosis. It may be used alone or with other drugs. Ribavirin is an antiviral medication used to treat HCV infection. It is not effective when used alone and must be used in combination with other medications, such as sofosbuvir. This study pertains to a comprehensive assessment of the deleterious effects of sofosbuvir (an antiviral drug against chronic HCV) or sofosbuvir combined with ribavirin (an antiviral drug against RNA and DNA viruses) on several biological activities of the body, including hematological, hormonal, biochemical, histological, and immunohistochemical examinations during a long-standing period on male healthy rats. In addition, fertility assessments were performed, including sperm collections and semen parameter investigations. This study was conducted on 21 male rats divided into three equal groups. Group I (control group) received distilled water; group II (sofosbuvir group) received sofosbuvir (4 mg/kg); and group III (sofosbuvir + ribavirin) received sofosbuvir (4 mg/kg) plus ribavirin (30 ml/kg). All groups received the specific drug for six months. Blood and tissue samples were collected for hematological, hormonal, biochemical, histological, and immunohistochemical examinations. In addition, sperm collection and assessments of semen parameters were performed. Results revealed that sofosbuvir causes a highly significant decrease in the mean of most hematological, immunological, hormonal, and biochemical parameters, except for a few numbers of parameters such as neutrophils, monocytes, basophils, cortisol, GOT, and lipase, which exhibit a significant increase. The same occurred in the sofosbuvir + ribavirin group, but at much higher levels, as most hematological, immunological, hormonal, and biochemical parameters exhibit a highly significant decrease except for monocytes, triglyceride, and lipase, which exhibit a significant increase. When compared to the sofosbuvir group alone, the sofosbuvir + ribavirin group demonstrated a highly significant decline in the mean of most hematological, immunological, hormonal, and biochemical parameters except lymphocytes and triglycerides, which exhibit a substantial increase. For the reproductive parameters, both groups exhibit a significant decrease in the total sperm motility percentage. Finally, it can be concluded that sofosbuvir causes acute pancreatitis and combined immunodeficiency. Ribavirin is associated with hormonal deficiency, which indicates the occurrence of hypopituitarism. Moreover, sofosbuvir and ribavirin synergistically affect myelosuppression and cause iron-deficiency anemia. However, sofosbuvir, or its combination with ribavirin, is associated with a reduced risk of hepatocellular carcinoma. Besides, adding ribavirin to be combined with sofosbuvir improved the immunodeficiency caused by sofosbuvir; this confirms that using ribavirin with sofosbuvir reduces the side effects of both alone.

Protective effects of Folic acid against reproductive, hematological, hepatic, and renal toxicity induced by Acetamiprid in male Albino rats.

Acetamiprid (ACP) is a widespread used insecticide belonging to neonicotinoids (NNs) that are introduced for controlling pests, and for domestic use to control fleas on cats and dogs. The current experiment pertains to a comprehensive overview of the toxic effects of acetamiprid and the protective role of folic acid against reproductive, hematological, histopathological and biochemical toxicity induced by ACP during 5 weeks. Male Albino rats were divided into four groups of seven each: First group served as control rats (CL group); Second group received acetamiprid (ACP group) (10 mg/Kg body weight) by oral gavage. Third group received both acetamiprid and folic acid (ACP + FA group) (2 mg/Kg body weight); Fourth group received folic acid (FA group) (2 mg/Kg body weight). Exposure of rats to acetamiprid caused significant changes in the reproductive indices as it cause a significant decrease in the sperm count, viability and motility. Furthermore, reproductive hormones such as testosterone and gonadotropin-releasing hormones (GnRH) were found significantly decreased in acetamiprid treated group. In addition, acetamiprid administration causes significant changes of some hematological and immunological parameters (red blood cells (RBC), hemoglobin (Hb), platelet (Plt), white blood cells (WBCs), lymphocyte, monocyte, neutrophil, eosinophil, IgG, IgM and IgA) in treated rats compared to controls. Significant increases in the levels of hepatic markers enzymes (aspartate transaminase (AST), Alanine transaminase (ALT), alkaline phosphatase (ALP) in acetamiprid treated group, as well as severe toxic effect was found on the liver and kidney after acetamiprid delivery according to the histopathological examinations which were confirmed after applying histological, histochemical, and Immunohistochemistry tests. The most conspicuous histopathological changes occurred on the liver and kidney of the acetamiprid treated group represented in the liver by fatty liver cells, leukocytic infiltration, and hemorrhage while in kidney tissues revealed tubular atrophy, dense eosinophilic cytoplasm and dilated congested blood vessels. Both liver and kidney tissues showed an increase in the amount of collagenous fibers and immune reactivity of fatty acid synthase. Moreover, other markers such as uric acid and total antioxidant capacity (TAC) were significantly decreased in acetamiprid treated rats. Co-administration of folic acid to the third group restored all the parameters cited above to near-normal values. Therefore, our investigation revealed that acetamiprid induce severe toxicity on different body systems and parameters and folic acid appeared to be a promising agent for protection against acetamiprid-induced toxicity.