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

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Abstract

Background Overdoses of Panadol (APAP) result in hepatic and renal toxicity. Up till now, there is no effective drug for APAP-enhanced nephrotoxicity. This work aims to explore the protective effects of N-acetylcysteine, 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 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.

Original languageEnglish
Pages (from-to)1088-1093
Number of pages6
JournalPharmacological Reports
Volume69
Issue number5
DOIs
Publication statusPublished - 1 Oct 2017

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Acetaminophen
Down-Regulation
Antioxidants
Kidney
Curcumin
Thioctic Acid
Antidotes
Acetylcysteine
Uric Acid
Interleukin-1
Oxidants
Superoxide Dismutase
Glutathione
Urea
Creatinine
Tumor Necrosis Factor-alpha
Control Groups
Liver
Serum
Pharmaceutical Preparations

Keywords

  • Amelioration
  • Histopathology
  • Nephrotoxicity
  • Panadol
  • Wistar rat

Cite this

Al-Rasheed, Nouf ; Faddah, Laila M. ; Hasan, Iman H. ; Ali, Hanaa M. ; Al-Rasheed, Nawal ; El Oraby, Nagla F. ; Mohamed, Mahmoud H. / Amelioration of panadol-induced nephrotoxicity via down-regulation of Bax/Bcl2 ratio with some antioxidants. In: Pharmacological Reports. 2017 ; Vol. 69, No. 5. pp. 1088-1093.
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abstract = "Background Overdoses of Panadol (APAP) result in hepatic and renal toxicity. Up till now, there is no effective drug for APAP-enhanced nephrotoxicity. This work aims to explore the protective effects of N-acetylcysteine, 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 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.",
keywords = "Amelioration, Histopathology, Nephrotoxicity, Panadol, Wistar rat",
author = "Nouf Al-Rasheed and Faddah, {Laila M.} and Hasan, {Iman H.} and Ali, {Hanaa M.} and Nawal Al-Rasheed and {El Oraby}, {Nagla F.} and Mohamed, {Mahmoud H.}",
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Amelioration of panadol-induced nephrotoxicity via down-regulation of Bax/Bcl2 ratio with some antioxidants. / Al-Rasheed, Nouf; Faddah, Laila M.; Hasan, Iman H.; Ali, Hanaa M.; Al-Rasheed, Nawal; El Oraby, Nagla F.; Mohamed, Mahmoud H.

In: Pharmacological Reports, Vol. 69, No. 5, 01.10.2017, p. 1088-1093.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Amelioration of panadol-induced nephrotoxicity via down-regulation of Bax/Bcl2 ratio with some antioxidants

AU - Al-Rasheed, Nouf

AU - Faddah, Laila M.

AU - Hasan, Iman H.

AU - Ali, Hanaa M.

AU - Al-Rasheed, Nawal

AU - El Oraby, Nagla F.

AU - Mohamed, Mahmoud H.

PY - 2017/10/1

Y1 - 2017/10/1

N2 - Background Overdoses of Panadol (APAP) result in hepatic and renal toxicity. Up till now, there is no effective drug for APAP-enhanced nephrotoxicity. This work aims to explore the protective effects of N-acetylcysteine, 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 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.

AB - Background Overdoses of Panadol (APAP) result in hepatic and renal toxicity. Up till now, there is no effective drug for APAP-enhanced nephrotoxicity. This work aims to explore the protective effects of N-acetylcysteine, 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 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.

KW - Amelioration

KW - Histopathology

KW - Nephrotoxicity

KW - Panadol

KW - Wistar rat

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U2 - 10.1016/j.pharep.2017.04.019

DO - 10.1016/j.pharep.2017.04.019

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JO - Pharmacological Reports

JF - Pharmacological Reports

SN - 1734-1140

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