Abstract
BackgroundTamiflu/oseltamivir phosphate (OP), an anti-influenza drug, has a highly doubted safety especially after many cases of abnormal behaviour and deaths reported after being used. Such controversy was also locally and globally generated, especially after being heavily used in COVID-19 treatment protocol. This study was designed to evaluate the effect of three different doses of OP on the liver and kidneys of male adult albino rats through histological approaches, measuring their DNA integrity and biochemical analyses. Different doses of Tamiflu applied to humans were converted to rats, then observed their effects on the liver and kidneys. Rats were divided into four groups. G1: considered as control group. The rest of the three treated groups were received the same calculated dose of Tamiflu (6.75 mg/kg b.w.) in three different durations. G2, G3 and G4 represented the animals orally received OP, in which the rats received OP twice for 5 consecutive days, once for 10 and 45 days, respectively.ResultsOur data showed numerous deleterious necrotic and fibrotic histopathological changes in the liver, and kidneys; as well as necrotic DNA smears, by using electrophoresis, in OP-treated rats of G2 and G4. In addition, OP significantly increased the serum cellular hepatic/renal toxicity markers (ALT, AST, ALP, GGT, indirect bilirubin, urea, creatinine, uric acid, & Na+). Also, it showed a reduction in the levels of serum total protein, albumin and K+ ions in rats of G2 and G4 compared with G1. In G3, OP treatment did not significantly alter hepatic/renal histological, DNA integrity and biochemical analyses in rats. ConclusionsThe therapeutic and long-term prophylactic doses of OP most likely cause structural and functional hepato- and nephrotoxicity in experimentally subjected rats. So, caution must be taken during Tamiflu treatment, and not used for long durations and/or with repetitive doses (time- and/or accumulative-dose-dependent); especially with patients suffer from liver and/or kidney dysfunction, while the short-term prophylactic dose of OP appears to be relatively safe and could be explored for oral medications.Graphical
Highlights
Tamiflu/oseltamivir phosphate (OP), an anti-influenza drug, has a highly doubted safety especially after many cases of abnormal behaviour and deaths reported after being used
Non-homogeneous and sever picture of alterations was observed in group 4
Our biochemical findings showed significant increases in the serum toxicity markers of both liver and kidneys (ALT, Aspartate aminotransferase (AST), alkaline phosphatase (ALP), GGT, indirect bilirubin, urea, creatinine, uric acid and Na+), which were accompanied by decreases in the levels of serum total protein, albumin and K + ions of Group 2 (G2) (The therapeutic dose) and Group 4 (G4)
Summary
Tamiflu/oseltamivir phosphate (OP), an anti-influenza drug, has a highly doubted safety especially after many cases of abnormal behaviour and deaths reported after being used. Such controversy was locally and glob‐ ally generated, especially after being heavily used in COVID-19 treatment protocol. This study was designed to evalu‐ ate the effect of three different doses of OP on the liver and kidneys of male adult albino rats through histological approaches, measuring their DNA integrity and biochemical analyses. In 1998, Mendel et al [1] stated that Tamiflu is designed to be highly specific to the influenza virus Due to this high specificity, it was suggested that Tamiflu would be effective in the treatment of the coronavirus. Others reported that Tamiflu administration cause several adverse effects on many vital organs [10,11,12,13,14]
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