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Nootkatone Supplementation Attenuates Carbon Tetrachloride Exposure-Induced Nephrotoxicity in Mice.

ABSTRACT: Nootkatone (NKT), a major ingredient of Alpinia oxyphylla, exhibited potential nephroprotective effects; however, the precise molecular mechanisms remain poorly understood. This study aimed to study the nephroprotective effects of NKT and the underlying mechanisms in a mouse model. Our results showed that NKT pretreatment at the doses of 5, 10, and 20 mg/kg per day for 7 days significantly attenuates carbon tetrachloride (CCl₄)-induced increases of serum BUN and CRE and kidney pathology injury. NKT pretreatment also markedly inhibited oxidative stress, inflammatory response, and the activation of caspases-9 and -3 in kidneys of mice exposed to CCl₄. Meanwhile, NKT pretreatment downregulated the expression of NOX4, IL-1β, IL-6, and TNF-α proteins and NO levels in the kidney tissues. Moreover, NKT pretreatment upregulated the expression of Nrf2 and HO-1 mRNAs, and downregulated the expression of NF-κB, IL-1β, IL-6, TNF-α, and iNOS mRNAs in the kidneys of mice, compared to those in the CCl₄ alone treatment group. In conclusion, our results reveal that NKT supplementation could protect against CCl₄ exposure-induced oxidative stress and inflammatory response in the kidneys by inhibiting NOX4 and NF-κB pathways and activating the Nrf2/HO-1 pathway. Our current study highlights the therapeutic application of NKT for kidney diseases.

SUBMITTER: Dai C

PROVIDER: S-EPMC9951873 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Nootkatone Supplementation Attenuates Carbon Tetrachloride Exposure-Induced Nephrotoxicity in Mice.

Dai Chongshan C Liu Mingchao M Zhang Qinzhi Q Das Gupta Subhajit S Tang Shusheng S Shen Jianzhong J

Antioxidants (Basel, Switzerland) 20230203 2

Nootkatone (NKT), a major ingredient of Alpinia oxyphylla, exhibited potential nephroprotective effects; however, the precise molecular mechanisms remain poorly understood. This study aimed to study the nephroprotective effects of NKT and the underlying mechanisms in a mouse model. Our results showed that NKT pretreatment at the doses of 5, 10, and 20 mg/kg per day for 7 days significantly attenuates carbon tetrachloride (CCl<sub>4</sub>)-induced increases of serum BUN and CRE and kidney patholo ...[more]

PMID: 36829928

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Project description:BackgroundHydrogen sulfide (H(2)S) displays vasodilative, anti-oxidative, anti-inflammatory and cytoprotective activities. Impaired production of H(2)S contributes to the increased intrahepatic resistance in cirrhotic livers. The study aimed to investigate the roles of H(2)S in carbon tetrachloride (CCl(4))-induced hepatotoxicity, cirrhosis and portal hypertension.Methods and findingsSodium hydrosulfide (NaHS), a donor of H(2)S, and DL-propargylglycine (PAG), an irreversible inhibitor of cystathionine ?-lyase (CSE), were applied to the rats to investigate the effects of H(2)S on CCl(4)-induced acute hepatotoxicity, cirrhosis and portal hypertension by measuring serum levels of H(2)S, hepatic H(2)S producing activity and CSE expression, liver function, activity of cytochrome P450 (CYP) 2E1, oxidative and inflammatory parameters, liver fibrosis and portal pressure. CCl(4) significantly reduced serum levels of H(2)S, hepatic H(2)S production and CSE expression. NaHS attenuated CCl(4)-induced acute hepatotoxicity by supplementing exogenous H(2)S, which displayed anti-oxidative activities and inhibited the CYP2E1 activity. NaHS protected liver function, attenuated liver fibrosis, inhibited inflammation, and reduced the portal pressure, evidenced by the alterations of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), albumin, tumor necrosis factor (TNF)-?, interleukin (IL)-1?, IL-6 and soluble intercellular adhesion molecule (ICAM)-1, liver histology, hepatic hydroxyproline content and ?-smooth muscle actin (SMA) expression. PAG showed opposing effects to NaHS on most of the above parameters.ConclusionsExogenous H(2)S attenuates CCl(4)-induced hepatotoxicity, liver cirrhosis and portal hypertension by its multiple functions including anti-oxidation, anti-inflammation, cytoprotection and anti-fibrosis, indicating that targeting H(2)S may present a promising approach, particularly for its prophylactic effects, against liver cirrhosis and portal hypertension.

Dataset Information

Nootkatone Supplementation Attenuates Carbon Tetrachloride Exposure-Induced Nephrotoxicity in Mice.

Publications

Nootkatone Supplementation Attenuates Carbon Tetrachloride Exposure-Induced Nephrotoxicity in Mice.

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