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.

Spinosad (SPD) is a highly selective insect control product. However, it was reported that SPD has toxicity toward other non-target organisms. This study was conducted to address the toxic effect of two sub-chronic low and high doses; 35 and 350 mg/kg SPD on some biochemical, histological and immunohistochemical parameters of the liver, kidney and cerebellum. Thirty-six male Swiss mice were divided into three groups of 12 mice each; first group (G1) served as a control, second group (G2) received a low sub-chronic dose of SPD that is equal to 35 mg/kg, and third group (G3) received a high sub-chronic dose of SPD that is equal to 350 mg/kg. The results showed that mice which were received 350 mg/kg SPD showed a significant decrease in the body weight and a significant increase in their relative kidney and spleen weights. They also showed a significant increase in alanine aminotransferase (ALT), triglycerides and urea levels. Histopathological examination showed cytoplasmic degeneration and cell necrosis in the liver and kidney. Immunohistochemical examination showed that cerebellum illustrated several neurodegenerative changes and a down-regulation of synaptophysin-Syp. In conclusion, exposure to a high dose of SPD that is equal to 350 mg/kg could cause a marked toxicity on the liver, kidney and cerebellum in male albino mice.

Background: Hypothyroidism is a decrease in the production of the thyroid hormones and leads to gland dysfunction. Spirulina used as an antioxidant and supposed as antihypothyroidic agent. Objective: This study was carried out to investigate the impact of Spirulina on PTU-induced hypothyroidism in rats. Materials and Methods: The rats were divided into six groups, control group (G1), hypothyroid group (G2), SP-500 treated group (G3), SP-1000 treated group (G4), PTU+SP-500 treated group (G5) and PTU+SP-1000 treated group (G6). Thyroid gland was examined using biochemical, histological, and immunohistochemical studies. Duration of treatments were for 14 days. Results: A significant decline in the body weight gain was exhibited. Biochemically, a significant decrease in T3 and T4 hormone levels in the PTU-group and a substantial increase in groups treated with Spirulina alone. While PTU+ Spirulina treated groups revealed normal hormonal levels more or less similar to the control group. Histological changes such as congestion of the blood capillaries, follicular dilatation, and vacuolar degeneration of some follicular cells were exhibited in hypothyroid group G2 and Spirulina treated-groups (G3andG4). Hyperplastic cells with hyperchromatic nuclei, depleted vacuolated-thyroglobulin, and a significant increase in the epithelial heights and the follicular diameters, were observed. Immunohistochemically, low expression of the proliferative cellular marker KI-67 was expressed in the PTU and PTU+Spirulina treated groups. While negative expression of KI-67 in Spirulina treated groups was recorded. Conclusion: Administration of Spirulina alone displayed signs of hyperactivity on the thyroid gland, but it has a mild protective role in the PTU-induced hypothyroidism groups. Therefore, caution should be used in extrapolating these results to the human being situation within different doses and durations.

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Hepatocellular carcinoma (HCC) is one of the world’s most widely recognized malignant tumors that accounts for 90% of all the primary liver cancers and is a major cause of death from cancer, representing half a million deaths per year. Obesity and associated metabolic irregularities, particularly diabetes mellitus (DM) and insulin resistance, are important risk factors for the advancement of HCC. Recently, retrospective studies showed that metformin (MET) could protect the hepatic tissues in pre-existing diabetes mellitus from HCC. The purpose of this study was to assess the role of MET treatment in the pre-existing diabetic rats before and after HCC induction by diethylnitrosamine (DEN). Thirty-five male Sprague Dawley albino rats were partitioned into the following groups: Group 1 (Gp1) was the control. Gp2 was injected intraperitoneally (i.p) with streptozotocin (STZ) (80 mg/kg) and DEN (50 mg/kg/7 weeks). Gp3, Gp4, and Gp5 were injected as in Gp2 and treated with MET (150 mg/kg) before and/or after HCC induction. Biochemical parameters including liver functions, lipid profile, and oxidative stress biomarkers were determined. Furthermore, histological and immunohistochemical changes were assessed in all groups. Our results illustrated that the group of rats that were treated with STZ and DEN had significant changes in both liver functions and were associated with alterations in the liver histopathological architectures. Treatment with MET before or after HCC induction ameliorated the cellular changes in the liver tissues; however, the utmost protection was found in a group of rats, which were treated with MET before and after HCC induction.

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Background: Spirulina is a biomass of cyanobacteria (blue-green algae) that can be consumed by humans and other animals. It is a type of microscopic algae in the shape of a perfect spiral coil. It is one of the many dietary supplements commercially available. It contains an abundant amount of essential amino acids, fatty acids, protein, vitamins, minerals, and pigments. Spirulina has many health benefits in preventing or managing hypercholesterolemia, hyperglycemia, cardiovascular diseases, diabetes, and other metabolic disease. Aim: The principal objective of this study was to estimate the possible side effects of two doses (500 and 1000 mg/kg b. wt) of Spirulina supplementation on as the liver, kidney and testis of rats. Materials and Methods: Adult male albino rats (Rattus norvegicus) weighing 120-140g were divided into three groups, G1: control; G2: treated with Spirulina at 500 mg/kg b. wt; and G3: treated with Spirulina at 1000 mg/kg b. wt. The administration was undertaken by gastric tube for 21 days. Biochemical analysis was done for measuring the blood levels of ALT, AST, urea, and creatinine. The liver, kidney and testis were excised, sectioned, and stained with different histological and histochemical stains for histopathological studies. Results: Spirulina induced many histological changes in the hepatic, renal, and testicular tissues, as well as biochemical changes in a dose-dependent manner. Conclusion: Uptake of uncontrolled supplementary doses of Spirulina may induce biochemical dysfunction and histopathological changes in some vital organs. Therefore, caution must be taken at using Spirulina as a food supplement. In fact, further biochemical and histopathological studies on its effect on other vital organs are needed for optimal dose-finding that should be considered for both efficacy and toxicity of Spirulina on the human body.