Suppression of glomerular damage and apoptosis and biomarkers of acute kidney injury induced by acetaminophen toxicity using a combination of resveratrol and quercetin

Dallak, Mohammad; Dawood, Amal F; Haidara, Mohamed A; Kader, Dina H Abdel; Eid, Refaat A.; Kamar, Samaa S; Eldeen, Asmaa M Shams

doi:10.1080/01480545.2020.1722156

Cited by 23 publications

(20 citation statements)

References 30 publications

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“…In the present study, APAP-treated rats showed a significant increase in levels of MDA, in the rat liver and kidney tissues which was reduced by co-treatment of animals by FA significantly. Dallak et al [13] suggested a relationship between APAP toxicity and increased MDA level and decreased GSH level. In our study, MDA levels in liver and kidney tissues were found to be significantly highest in APAP group compared to the other experimental groups.…”

Section: Discussionmentioning

confidence: 99%

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The potential protective role of folic acid against acetaminophen-induced hepatotoxicity and nephrotoxicity in rats

2021

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Folic acid (FA), is a group B vitamin, has high reactive oxygen radicals quenching ability, resulting in protection against oxidative damage in aerobic cell. Acetaminophen (N-acetyl-paminophenol, APAP) is a nonsteroidal anti-inflammatory drug, and can promote oxidative damage in liver and kidney tissues. The aim of this study was to investigate whether folic acid has protective effects on oxidative liver and kidney injury caused by experimental APAP toxication. Forty female Sprague dawley rats were divided into 5 groups; control, APAP, FA, APAP+FA, and APAP+N-acetylcysteine (NAC) groups. APAP toxication was induced by oral gavage (3 g/kg bodyweight). FA (20 mg/kg bodyweight) and NAC (150 mg/kg bodyweight) were given by oral gavage to the specified groups. Oxidant and antioxidant parameter were determined in liver and kidney tissues. In addition, the liver and kidney tissues were histological evaluated. When compared with APAP group, superoxide dismutase (SOD) and catalase activities and glutathione levels were statistically higher, malondialdehyde (MDA) level and myeloperoxidase activity (except liver tissue) were statistically lower in both APAP+FA and APAP+NAC. Liver and kidney MDA level and kidney SOD activity were significantly lower in APAP+NAC group compared with APAP+FA group. Co-administration of NAC with APAP was found to provide protection, but hepatic cords were defective in some places and some glomerular tubules also had dilatation. Necrotic areas was reduced in the liver and the glomerular structure was in good condition in the APAP+FA group. As a result, FA might have a protective effect against APAP-induced hepato-nephrotoxicity and oxidative stress in rat.

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Section: Discussionmentioning

confidence: 99%

“…Because NAC promotes GSH synthesis in the liver and renews GSH stores. Many compounds such as vitamins [11,12] and antioxidants [13] have been used for their protective effects against APAP toxicity. Therefore, new treatment modalities in APAP poisoning cases are still of interest.…”

Section: Introductionmentioning

confidence: 99%

The potential protective role of folic acid against acetaminophen-induced hepatotoxicity and nephrotoxicity in rats

2021

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“…Resveratrol is a natural polyphenolic chemical found in high amounts in red grape skins and seeds 17 . It is a pleotropic compound that has many benefits which is reported to protect the cardiovascular, 18 renal, 19 pancreas, 20 and ovary 21 . Resveratrol also has anti‐inflammatory effects, 22 inhibits lipid peroxidation, 23 inhibits platelet aggregation and thrombus formation, 24 and promotes cell survival and prevention of apoptosis 25,26 .…”

Section: Introductionmentioning

confidence: 99%

Resveratrol suppresses cholestasis‐induced liver injury and fibrosis in rats associated with the inhibition of TGFβ1–Smad3–miR21 axis and profibrogenic and hepatic injury biomarkers

ShamsEldeen

Ebrahim

Rashed

et al. 2021

Clin Exp Pharma Physio

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Cholestasis caused by slowing or blockage of bile flow is a serious liver disease that can lead to liver fibrosis and cirrhosis. The link between transforming growth factor beta 1 (TGFβ1), Smad family member 3 (Smad3), and microRNA 21 (miR21) in bile duct ligation (BDL)‐induced liver fibrosis in the presence and absence of the anti‐inflammatory and antioxidant compound, resveratrol (RSV), has not been previously studied. Therefore, we tested whether RSV can protect against BDL‐induced liver fibrosis associated with the inhibition of the TGFβ1–Smad3–miR21 axis and profibrogenic and hepatic injury biomarkers. The model group of rats had their bile duct ligated (BDL) for 3 weeks before being killed, whereas, the BDL‐treated rats were separated into three groups that received 10, 20, and 30 mg/kg RSV daily until the end of the experiment. Using light microscopy and ultrasound examinations, we documented in the BDL group, the development of hepatic injury and fibrosis as demonstrated by hepatocytes necrosis, bile duct hyperplasia, collagen deposition, enlarged liver with increased echogenicity, irregular nodular border and dilated common bile duct, which were more effectively inhibited by the highest used RSV dosage. In addition, RSV significantly (p ≤ 0.0027) inhibited BDL‐induced hepatic TGFβ1, Smad3, miR21, the profibrogenic biomarker tissue inhibitor of metalloproteinases‐1 (TIMP‐1), malondialdehyde (MDA), interleukin‐17a (IL‐17a), and blood levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin. These findings show that RSV at 30 mg/kg substantially protects against BDL‐induced liver injuries, which is associated with the inhibition of TGFβ1‐Smad3‐miR21 axis, and biomarkers of profibrogenesis, oxidative stress, and inflammation.

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“…Quercetin has therapeutic potential in cases of renal damage [91,92]. Previous studies have concluded that quercetin may effectively treat renal injury caused by chemical compounds that induce hypoxia [30,32,93,94]. In the present study, we used quercetin as a natural agent to reduce indomethacin-induced renal injury.…”

Section: Discussionmentioning

confidence: 96%

“…Flavonoids have been reported to be potential antioxidant chemopreventive agents [27][28][29]. In particular, quercetin has shown protective in vitro and in vivo abilities against chemically induced acute kidney damage by inducing antioxidant, inflammatory, and glomerular ultrastructural effects [30][31][32][33][34].…”

Section: Introductionmentioning

confidence: 99%

Effect of Quercetin on Injury to Indomethacin-Treated Human Embryonic Kidney 293 Cells

Chen

Yang

et al. 2021

Life

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Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat inflammation and pain and even to prevent the progression of cardiovascular disease. They have become widely used because of their effectiveness, especially among athletes performing high-intensity training. Indomethacin is used for pain management in sports medicine and is highly effective and versatile. However, several clinical studies have reported that indomethacin induces acute renal damage. In the present study, we determined that indomethacin reduced human embryonic kidney 293 (HEK293) cell viability in a concentration-dependent manner by triggering apoptosis. In addition, we demonstrated the effect of quercetin on indomethacin-treated HEK293 cells by inactivating the caspase-3 and caspase-9 signals. Furthermore, quercetin reduced ROS production and increased mitochondrial membrane potential (ΔΨm) in indomethacin-treated HEK293 cells. Our results indicate that quercetin can interrupt the activated caspase and mitochondrial pathway induced by indomethacin in HEK293 cells and affect apoptotic mRNA expression. Quercetin can protect against indomethacin-induced HEK293 cell apoptosis by regulating abnormal ΔΨm and apoptotic mRNA expression.

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Suppression of glomerular damage and apoptosis and biomarkers of acute kidney injury induced by acetaminophen toxicity using a combination of resveratrol and quercetin

Cited by 23 publications

References 30 publications

The potential protective role of folic acid against acetaminophen-induced hepatotoxicity and nephrotoxicity in rats

The potential protective role of folic acid against acetaminophen-induced hepatotoxicity and nephrotoxicity in rats

Resveratrol suppresses cholestasis‐induced liver injury and fibrosis in rats associated with the inhibition of TGFβ1–Smad3–miR21 axis and profibrogenic and hepatic injury biomarkers

Effect of Quercetin on Injury to Indomethacin-Treated Human Embryonic Kidney 293 Cells

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