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Published on: November 27, 2019
Pathophysiological effects of Tamiflu on liver and kidneys of male rats
Wafaa H Abdel-Ghaffar1, Eman A Abdelghffar1,2
1Department of Zoology, Faculty of Science, Ain Shams University, Cairo, Egypt.
Background:
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 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.
Results:
Our 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.
Conclusions:
The 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.
Insights
Tamiflu (oseltamivir phosphate) caused liver and kidney damage in rats with long-term or repeated use. Short-term Tamiflu prophylaxis appears relatively safe, but caution is advised for patients with existing liver or kidney issues.
Area of Science:
- Pharmacology and Toxicology
- Histopathology
- Biochemistry
Background:
- Oseltamivir phosphate (Tamiflu) is an anti-influenza medication with debated safety, particularly concerning adverse events and its use in COVID-19 protocols.
- Concerns regarding Tamiflu's safety profile have been raised globally due to reported adverse effects.
Purpose of the Study:
- To investigate the histological and biochemical effects of different oseltamivir phosphate (OP) doses on the liver and kidneys of male adult albino rats.
- To assess the impact of varying durations of OP administration on DNA integrity and key toxicity markers.
Main Methods:
- Rats were divided into control and three treatment groups receiving a calculated dose of OP (6.75 mg/kg b.w.) for different durations: 5 days (twice daily), 10 days (once daily), and 45 days (once daily).
- Histopathological examination, DNA integrity analysis (electrophoresis), and serum biochemical analyses were performed to evaluate liver and kidney function and damage.
Main Results:
- Long-term (45 days) and repeated (5 days twice daily) OP administration induced significant histopathological damage (necrosis, fibrosis) and DNA fragmentation in the liver and kidneys.
- OP treatment significantly elevated serum hepatic/renal toxicity markers (ALT, AST, ALP, GGT, bilirubin, urea, creatinine, uric acid, Na+) and decreased total protein, albumin, and K+ levels in the affected groups.
- Short-term (10 days once daily) OP treatment did not cause significant alterations in hepatic/renal histology, DNA integrity, or biochemical parameters.
Conclusions:
- Therapeutic and long-term prophylactic doses of oseltamivir phosphate (OP) can cause significant hepato- and nephrotoxicity in rats, indicating a potential risk with prolonged or repetitive use.
- Caution is recommended when using Tamiflu, especially in patients with pre-existing liver or kidney conditions, due to potential time- and dose-dependent toxicity.
- Short-term prophylactic use of OP demonstrated relative safety and warrants further exploration for oral medication applications.
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