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Lead (Pb) is a common pollutant that is not biodegradable and gravely endangers the environment and human health. Annona squamosa fruit has a wide range of medicinal uses owing to its phytochemical constituents. This study evaluated the effect of treatment with A. squamosa fruit extract (ASFE) on testicular toxicity induced in male rats by lead acetate. The metal-chelating capacity and phytochemical composition of ASFE were determined. The LD50 of ASFE was evaluated by probit analysis. Molecular docking simulations were performed using Auto Dock Vina. Forty male Sprague Dawley rats were equally divided into the following groups: Gp1, a negative control group; Gp2, given ASFE (350 mg/kg body weight (b. wt.)) (1/10 of LD50); Gp3, given lead acetate (PbAc) solution (100 mg/kg b. wt.); and Gp4, given PbAc as in Gp3 and ASFE as in Gp2. All treatments were given by oro-gastric intubation daily for 30 days. Body weight changes, spermatological parameters, reproductive hormone levels, oxidative stress parameters, and inflammatory biomarkers were evaluated, and molecular and histopathological investigations were performed. The results showed that ASFE had promising metal-chelating activity and phytochemical composition. The LD50 of ASFE was 3500 mg/kg b. wt. The docking analysis showed that quercetin demonstrated a high binding affinity for JAK-1 and STAT-3 proteins, and this could make it a more promising candidate for targeting the JAK-1/STAT-3 pathway than others. The rats given lead acetate had defective testicular tissues, with altered molecular, biochemical, and histological features, as well as impaired spermatological characteristics. Treatment with ASFE led to a significant mitigation of these dysfunctions and modulated the JAK-1/STAT-3/SOCS-1 axis in the rats. [ABSTRACT FROM AUTHOR]

Background: Several studies have found an association between Diabetes mellitus (DM) and an increased risk for hepatocellular carcinoma (HCC). Evidence suggests that Metformin (Met) may have a therapeutic and protective effect against both DM and HCC. Therefore, the aim of this study was to evaluate the antioxidant effect of Met against DM and HCC-induced oxidative stress in rat model. Methods: Forty-two male albino rats were randomly divided into six groups. Group 1 (Gp1) was the control group, Gp2 received an intraperitoneal (i.p.) injection with streptozotocin (STZ), Gp3 was injected i.p. with diethyl nitrosamine (DEN), Gp4 received an oral administration of Met, Gp5 and Gp6 received the same injections as Gp2 and Gp3, respectively, then received an additional injection of Met. Oxidative stress biomarkers, including superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and malondialdehyde (MDA), were examined. Furthermore, biochemical parameters including liver function tests were assessed. Histopathological and immunohistochemical alterations of the liver were also examined. Results: Our results demonstrate that Gp2 and Gp3 had significant signs of liver dysfunction and had elevated levels of MDA and reduced levels of SOD, CAT, and GSH. Additionally, Gp2 and Gp3 showed significant alterations in the liver architecture shown by high PCNA and caspase-3 expression. In the Gp5 and Gp6, treatment with Met showed an improvement in liver function, oxidative stress biomarkers, and reduced histopathological changes in hepatocytes. Conclusions: This study offers insight into the potential for Metformin as a novel therapeutic against the oxidative stress induced by DM or HCC. [ABSTRACT FROM AUTHOR]