Abstract
Abstract Objectives Acute kidney injury (AKI) is a critical clinical event characterized by a reduction in the excretory function of the kidneys. N-acetylcysteine (NAC), N-acetylmethionine (NAM) and N-acetylglucosamine (NAG) are antioxidants with scanty known genetic mechanisms. We aimed to assess both kidney injury molecule-1 (KIM-1) and growth-arrested DNA damage-inducible gene-153 (GADD-153) genes expression in paracetamol (PA) induced AKI. Also, to recognize whether NAC, NAM and/or NAG have roles in altering the expression of these genes for ameliorating the AKI induced by PA. Methods The present preliminary study achieved the AKI model by oral administration of PA therapeutic dose for 15 days in experimental male rats. Serum urea, creatinine, and renal oxidative stress parameters were analyzed. Genetic expression of KIM-1 and GADD-153 were determined using real time-PCR. Results Significant elevations of serum urea, creatinine and nitric oxide in renal tissue after PA administration; however, total thiol content was reduced. In addition, both KIM-1 and GADD-153 were upregulated. These biochemical alterations were improved after using NAC and partially after NAM; however, NAG had little effect. Conclusions Up-regulation of both KIM-1 and GADD-153 occur in AKI induced by PA, which was significantly reversed by NAC.
Highlights
Acute kidney injury (AKI) is a sudden onset of renal damage or dysfunction and it occurs due to either pre-renal, renal, or post renal causes [1].Paracetamol (PA) is a non-steroidal analgesic and antipyretic drug
TJB-2021-0233_proof ■ 27 December 2021 ■ 6:19 am Mohamed et al.: Genetic mechanism of antioxidants in reversing paracetamol-induced renal damage changed to the nephrotoxic component, p-aminophenol (PAP), which is similar to N-acetyl-p-benzoquinone imine (NAPQI) in its way of excretion; in case of reduction of reduced glutathione (GSH), PAP causes cytotoxicity to the kidney [2]
The proposed mechanism was correlated to the chemical structure of kidney injury molecule-1 (KIM-1), where following AKI, the extracellular part of KIM-1 shed into extracellular space of renal tubules, and it released in urine in excess amount compared to the normal condition [21], and such pathway is regulated via mitogen-activated protein kinase (MAPK) pathway
Summary
Acute kidney injury (AKI) is a sudden onset of renal damage or dysfunction and it occurs due to either pre-renal, renal, or post renal causes [1].Paracetamol (PA) is a non-steroidal analgesic and antipyretic drug. Acute kidney injury (AKI) is a sudden onset of renal damage or dysfunction and it occurs due to either pre-renal, renal, or post renal causes [1]. TJB-2021-0233_proof ■ 27 December 2021 ■ 6:19 am Mohamed et al.: Genetic mechanism of antioxidants in reversing paracetamol-induced renal damage changed to the nephrotoxic component, p-aminophenol (PAP), which is similar to N-acetyl-p-benzoquinone imine (NAPQI) in its way of excretion; in case of reduction of reduced glutathione (GSH), PAP causes cytotoxicity to the kidney [2]. N-acetylglucosamine (NAG), an amino sugar, is a prominent precursor of glycosaminoglycans, proteoglycans and glycoproteins, and it is obtained as a result of acid hydrolysis of chitin in shrimp shells [7]. Growth arrested DNA damage-inducible gene-153 (GADD-153) is one of the proteins that are affected by endoplasmic reticulum stress that is produced from AKI [9]
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