Amelioration of Panadol-induced Nephrotoxicity via Down-regulation of Bax/Bcl2 Ratio with Some Antioxidants.
, . Nouf Al-Rasheed, Laila M. Faddah, Iman H. Hasan, Hanaa M. Ali, Nawal Al-Rasheed, Nagla F. El Oraby, Mahmoud H. Mohamed, . 2017
Abstract
Background: Overdoses of Panadol (APAP) result in hepatic and renal toxicity.
Up till now, there is no effective drug for APAP-enhanced nephrotoxicity.
Objective: This work aims to explore the protective effects of Nacetylcysteine,
Thymoquinone (THQ), Curcumin (CUR) and α-Lipoic acid (LA) either
alone or in combination against APAP nephrotoxicity, focused on modulation of
Bax/Bcl2 pathway.
Methods: APAP was administrated at a single dose then treated with the fore
mentioned antioxidants.
Results: APAP administration increased serum creatinine, urea, uric acid,
tumor necrosis factor-α (TNF –α), and interleukin-1β (IL-1β) levels compared to
control group. There is a marked depletion of reduced glutathione (GSH) levels and
superoxide dismutase activity (SOD), Bax level was overexpressed, whereas Bcl2 was
downregulated in renal tissue. Histopathological examination of the kidney tissue
supported these biochemical findings. Treatment with the fore mentioned anti-oxidants
2
ameliorated most of the previous evaluated parameters and returned the kidney nearly
to its normal architecture.
Conclusion: The expression of Bax and Bcl2 is considered one of the
mechanisms underlying APAP-induced nephrotoxicity. The administration of THQ
along with CUR could be a promising antidote for APAP renal damage through their
antioxidant potential.
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