The most costly spice in the world, Crocus sativus L. (C. sativus), has been used for more than 3,000 years. It has various beneficial applications in a range of fields, including aromas, colorants, and medications, but its usefulness as a food flavoring and coloring ingredient is the highest. Large quantities of by-products from the processing of saffron are typically thrown as unwanted bio-residues. This study’s goal was to assess and compare the nephroprotective effects of hydroethanolic extracts of C. sativus stigmas, tepals, and leaves on gentamicin (GM)-induced nephrotoxicity in rats. For that, we used a biochemical and histological investigation to propose new pharmaceutical valorizations. Based on the biochemical and histological analyses, it is concluded that all the studied parts of C sativus showed a renoprotective effect. Markedly, tepals revealed the most significant reduction of relative liver weight
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, water intake
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, plasma creatinine
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, plasma urea
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, plasma uric acid
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, urinary protein
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and albumin
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, and renal malondialdehyde (MDA)
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. In addition, C. sativus tepals caused a significant increase in body weight
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, urinary creatinine
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, creatinine clearance
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, and urinary urea
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compared with the gentamicin untreated (GM) group. This is confirmed by the histopathological study which shows that treatment with stigmas, tepals, and leaves preserved kidney morphology at the glomerular and tubular cell level. The studied extracts exhibit good recovery potential for nephrotoxicity induced by gentamicin. In order to create potent dietary supplements or phytomedicines, it would also be very interesting to confirm these actions through clinical research.