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Modulatory effect of 4-phenyl butyric acid on hyperoxaluria-induced renal injury and inflammation

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Abstract

Hyperoxaluria-associated deposition of calcium oxalate crystals results from oxalate-induced renal injury and inflammation. The present study was designed to evaluate the effect of 4-Phenyl butyric acid (4-PBA), a chemical chaperone, in ethylene glycol-induced hyperoxaluria and compare its effect with antioxidant, N-acetyl cysteine (NAC). Male Sprague–Dawley rats were given ethylene glycol in drinking water for 28 days to induce hyperoxaluria. 4-PBA and NAC were given by oral gavage. Effect of 4-PBA was analyzed in both prophylactic and curative regimens. After every 7 days, 24-h urine samples were analyzed for kidney injury and inflammation markers. Increased amounts of kidney injury markers like Kidney injury molecule-1, Lactate dehydrogenase, and N-acetyl-β-glucoseaminidase were found in the urine of hyperoxaluric rats which were significantly reduced by 4-PBA treatment in both prophylactic and curative regimens. Inflammatory markers IL-1β, IL-6, and MCP-1 were also raised in the urine of hyperoxaluric rats which were significantly decreased by 4-PBA treatment. Hyperoxaluria was accompanied with renal oxidative stress as reflected by decreased glutathione redox status and increased reactive oxygen species which was significantly reduced by 4-PBA treatment. Histological study with H&E and Pizzolato staining showed numerous calcium oxalate crystal deposits in the renal tissues of hyperoxaluric rats. However, no significant crystal deposits were seen in the 4-PBA-treated hyperoxaluric rats. N-acetyl cysteine treatment effectively decreased renal oxidative stress but did not alter the production of inflammatory markers. Collectively, the present study suggested the potential protective effect of 4-PBA in hyperoxaluria-induced renal injury and inflammation.

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Acknowledgements

The financial assistance provided by the Science and Engineering Research Board (SERB), Government of India, New Delhi is gratefully acknowledged.

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  1. Department of Biochemistry, Panjab University, Chandigarh, Chandigarh, 160014, India

    Minu Sharma, Amarjit S. Naura & S. K. Singla

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  1. Minu Sharma
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Sharma, M., Naura, A.S. & Singla, S.K. Modulatory effect of 4-phenyl butyric acid on hyperoxaluria-induced renal injury and inflammation. Mol Cell Biochem 451, 185–196 (2019). https://doi.org/10.1007/s11010-018-3405-x

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