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Hesperetin attenuates teicoplanin-induced acute kidney injury by mitigating oxidative stress and inflammation in Wistar rats

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Graphical abstract Abstract Objectives Renal failure has been reported in patients treated with teicoplanin (TEIC), a widely used antibiotic. Hesperetin, a flavonoid in citrus fruits, has been reported to possess nephroprotective effects. This study investigated the protective effect of hesperetin on TEIC-induced nephrotoxicity in rats. Methods Male Wistar rats (n  = 32, 144–180 g) were grouped into four groups of eight rats each. The control, group 1 received water, group 2 received 50 mg/kg of hesperetin orally, group 3 received 10 mg/kg of TEIC intraperitoneally and group 4 received 50 mg/kg of hesperetin and 10 mg/kg of TEIC. Administration was done for 21 days. Rats were sacrificed 24 h after the last administration, and the kidney was excised and used for biochemical assays. Results Administration of TEIC resulted in kidney injury that was characterized by significant increase in plasma urea and creatinine level relative to control group (P < 0.05). Additionally, a significant increase in the biomarkers of inflammation (NO, myeloperoxidase, TNF-α) and lipid peroxidation (malondialdehyde) of TEIC-treated rats was observed when compared to the control group. Furthermore, altered antioxidant status was observed following TEIC treatment. Activities of enzymic antioxidants (SOD, CAT, GPx, GST) and concentration of non-enzymic antioxidants (GSH and ascorbic acid) were downregulated. In comparison to the TEIC-treated group, the administration of hesperetin with TEIC significantly reduced all changes in the markers of kidney injury, inflammation and oxidative stress. Histopathological examination revealed that rats given TEIC showed increased glomerular size and considerable hydropic changes in the proximal convoluted tubules, whereas rats given HESP and TEIC showed only mildly enhanced glomerular size and hydropic modifications. Conclusion Hesperetin preserved the histo-architecture of the kidney. From this study, hesperetin offered a protective effect against TEIC-induced nephrotoxicity in rats. Significance statement One of the known hazards of TEIC, a frequently used antibiotic, has been renal failure, among others. This study sheds fresh light on the efficacy of hesperetin, a flavonoid found in many citrus fruits, for preventing TEIC-induced kidney damage by reducing oxidative stress and inflammation. Also, hesperetin should be considered as an alternate supplement against TEIC-induced kidney impairment. Furthermore, the data reported in this study will provide useful information for future research into the therapeutic benefits of hesperetin as an alternative therapy for renal damage.
Title: Hesperetin attenuates teicoplanin-induced acute kidney injury by mitigating oxidative stress and inflammation in Wistar rats
Description:
Graphical abstract Abstract Objectives Renal failure has been reported in patients treated with teicoplanin (TEIC), a widely used antibiotic.
Hesperetin, a flavonoid in citrus fruits, has been reported to possess nephroprotective effects.
This study investigated the protective effect of hesperetin on TEIC-induced nephrotoxicity in rats.
Methods Male Wistar rats (n  = 32, 144–180 g) were grouped into four groups of eight rats each.
The control, group 1 received water, group 2 received 50 mg/kg of hesperetin orally, group 3 received 10 mg/kg of TEIC intraperitoneally and group 4 received 50 mg/kg of hesperetin and 10 mg/kg of TEIC.
Administration was done for 21 days.
Rats were sacrificed 24 h after the last administration, and the kidney was excised and used for biochemical assays.
Results Administration of TEIC resulted in kidney injury that was characterized by significant increase in plasma urea and creatinine level relative to control group (P < 0.
05).
Additionally, a significant increase in the biomarkers of inflammation (NO, myeloperoxidase, TNF-α) and lipid peroxidation (malondialdehyde) of TEIC-treated rats was observed when compared to the control group.
Furthermore, altered antioxidant status was observed following TEIC treatment.
Activities of enzymic antioxidants (SOD, CAT, GPx, GST) and concentration of non-enzymic antioxidants (GSH and ascorbic acid) were downregulated.
In comparison to the TEIC-treated group, the administration of hesperetin with TEIC significantly reduced all changes in the markers of kidney injury, inflammation and oxidative stress.
Histopathological examination revealed that rats given TEIC showed increased glomerular size and considerable hydropic changes in the proximal convoluted tubules, whereas rats given HESP and TEIC showed only mildly enhanced glomerular size and hydropic modifications.
Conclusion Hesperetin preserved the histo-architecture of the kidney.
From this study, hesperetin offered a protective effect against TEIC-induced nephrotoxicity in rats.
Significance statement One of the known hazards of TEIC, a frequently used antibiotic, has been renal failure, among others.
This study sheds fresh light on the efficacy of hesperetin, a flavonoid found in many citrus fruits, for preventing TEIC-induced kidney damage by reducing oxidative stress and inflammation.
Also, hesperetin should be considered as an alternate supplement against TEIC-induced kidney impairment.
Furthermore, the data reported in this study will provide useful information for future research into the therapeutic benefits of hesperetin as an alternative therapy for renal damage.

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