000 a
999 _c16223
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040 _aAIKTC-KRRC
_cAIKTC-KRRC
100 _98813
_aMorsy, Mohamed Aly
245 _aProtection of hesperidin against methotrexate- induced nephrotoxicity may be mediated by Nrf2/HO-1 pathway
250 _aVol.55(4), Oct-Dec
260 _aKarnataka
_bAssociation of Pharmaceutical Teachers of India (APTI)
_c2021
300 _a1066-1073p.
520 _aBackground: Methotrexate (MTX), a successfully used chemotherapeutic in the treatment of various malignancies and autoimmune diseases, might cause severe nephrotoxicity. Here, we aimed at investigating possible nephroprotective effects of hesperidin (HES), a flavanone present in citrus fruits, against MTX-induced toxicity. Methods: Rats were divided into control, HES, MTX, and MTX/HES groups, where HES was administered in a dose of 100 mg/kg/day orally for 8 days and MTX in a single i.p. dose of 20 mg/kg on day 5 of the experiment. Results: Pretreatment with HES significantly improved MTXinduced deteriorated kidney function and structure, as well as reversed MTX effects on renal tumor necrosis factor (TNF)-α level and caspase 3 expression. MTX upregulated renal breast cancer resistance protein (BCRP); an efflux transporter that extrudes MTX from the kidney. Unfortunately, MTX/HES did not show a further increase in BCRP expression but rather showed downregulation. MTX also caused downregulation of renal nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1) expressions, whereas HES reversed the MTX effect and upregulated renal Nrf2/HO-1. Conclusion: HES conferred protection against MTX-mediated nephrotoxicity, at least in part via anti-inflammatory and anti-apoptotic mechanisms. Nrf2/HO-1 pathway, but not BCRP, may have a role in HES-induced nephroprotection against MTX toxicity.
650 0 _94639
_aPHARMACEUTICS
700 _915861
_a El-Sheikh, Azza Ali Kamel
773 0 _x0019-5464
_tIndian journal of pharmaceutical education and research
_dBengluru Association of Pharmaceutical Teachers of India (APTI)
856 _uhttps://www.ijper.org/sites/default/files/IndJPhaEdRes-55-4-1066.pdf
_yClick here
942 _2ddc
_cAR