TOXICOLOGICAL CHARACTERIZATION OF SODIUM METABISULFITE AND MITIGATION OF ITS EFFECTS BY STANDARDIZED Ginkgo biloba EXTRACT (EGb-761) IN A MOUSE MODEL

Abstract

Sodium metabisulfite (SMB), is a biocide and antioxidant agent generally used as a preservative in food and beverage industries, but can oxidize to harmful sulfite radicals. A standardized Ginkgo biloba (EGb-761) is well characterized, with 24% flavone glycosides (primarily quercetin, kaempferol and isorhamnetin) and 6% terpene lactones (2.8-3.4% ginkgolides A, B and C, and 2.6-3.2% bilobalide). Notably, Ginkgolide B and bilobalide account for about 0.8% and 3% of the total extract, respectively. EGb-761 has demonstrated potent antioxidant and anti-inflammatory activity, beneficial for the treatment of toxicants and diseases that exhibit oxidative stress and inflammation. The present study sought to investigate the putative ameliorative effects of EGb-761 against SMB-induced toxicity in mice. Thirty-two male Swiss white mice were randomized into control, SMB-treated, SMB + EGb-761-treated and EGb-761-treated groups. EGb-761 (100mg/kg/day) and SMB (98mg/kg/day) were administered by gastric gavage for 40 days. Body and relative organ weight, haematological profile, serum electrolytes and lipid profile, tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), IL-10, nitric oxide (NO),tissue malondialdehyde (MDA) and reduced (GSH) levels and organ damage and pathology have been estimated. Oral administration of EGb-761 restored SMB-induced decrease in body weight and prevented SMB-induced thrombocytopenia, leukocytosis and anaemia. Further, EGb-761-treatment protected against SMB-induced liver and kidney injury depicted by decreased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, bilirubin, creatinine, urea, uric acid and albumin. Furthermore, EGb-761 treatment attenuated SMB-driven dyslipidemia and metabolic acidosis. Besides, EGb-761 supplementation abrogated SMB-driven oxidative stress as depicted by stabilized GSH levels in the brain, liver, kidney, spleen, heart and lungs. SMB induced a significant increase of tissue levels of MDA, NO, IFN-γ and TNF-α were abrogated by EGb-761 treatment. Histopathological analysis revealed that exposure to SMB resulted in liver and kidney damage. It was noted that EGb-761 nullified those adverse pathological lesions. In conclusion, these results demonstrate that oral administration of standardized Ginkgo bilobaattenuated SMB-induced alteration of hematological parameters, metabolic acidosis, inflammatory responses, oxidative stress and organ damage. These findings provide a novel approach that can be optimized for preventing or treating exposure due to SMB toxicity