Moderation of doxorubicin-induced nephrotoxicity in Wistar rats by aqueous leaf-extracts of Chromolaena odorata and Tridax procumbens

Abstract

Background: The major draw-back of doxorubicin's use in chemotherapy is its toxicity on various organs including the kidneys. This study investigated the potential protective role of aqueous leaf-extracts of Chromolaena odorata and Tridax procumbens against nephrotoxicity induced by doxorubicin. Methods: To this end, their impact on plasma biomarkers of kidney function, as well as renal lipid profile, biomarkers of oxidative stress, electrolyte profile and activities of renal ATPases was monitored in doxorubicin treated rats. Metformin (250 mg/kg body weight, orally) and the extracts (50, 75 and 100 mg/kg, orally) were daily administered for 14 days; while nephrotoxicity was induced with doxorubicin (15 mg/kg, intra-peritioneally), once on the 12th day of study. Results: The plasma concentrations of creatinine, and urea; as well as the renal malondialdehyde, cholesterol, calcium and sodium concentrations in the Test control, were significantly ( P < .05) higher than those of all the other groups. However, the renal concentrations of ascorbic acid, chloride, magnesium and potassium, and the renal activities of catalase, glutathione peroxidase superoxide dismutase, Ca 2+ -ATPase, Mg 2+ -ATPase and Na + ,K + -ATPase in the Test control were significantly ( P < .05) lower than those of all the other groups. Conclusions: Pre-treatment with the extracts and metformin boosted endogenous antioxidants, and prevented doxorubicin-induced renal damage, as indicated by the attenuation of doxorubicin-induced renal oxidative stress, as well as the attenuation of doxorubicin-induced adverse alterations in renal cholesterol, ATPases and electrolyte balance, and plasma biomarkers of kidney function, and keeping them at near-normal values.

Restoration of plasma kidney and liver biomarkers in doxorubicin-treated Wistar rats by aqueous extracts of Pleurotus tuberregium sclerotia and Cnidoscolus aconitifolius leaves

“…This finding agrees with other reports of doxorubicin-induced elevation of plasma creatinine and urea levels (Öz and İlhan, 2006;Yilmaz et al, 2006;Ikewuchi et al, 2021c). Because of their inverse relationship with glomerular function, plasma biomarkers such as creatinine and urea concentrations are usually monitored to evaluate glomerular function (Crook, 2012;Lamb and Price, 2015;Meisenberg and Simmons, 2017;Lieberman and Peet, 2018;Ikewuchi et al, 2021c). Therefore, the reduction in plasma creatinine and urea levels by the extracts is suggestive of their capacity to protect nephrons from doxorubicin-induced damage (Jambhulkar et al, 2014) and thus preserve the functional capacity of the glomerular filtration system (Ikewuchi et al, 2021c).…”

“…Doxorubicin is a well-established and highly effective anti-neoplastic agent that is used to treat several adult and paediatric cancers such as solid tumours, leukaemia, lymphomas, and breast cancer (Carvalho et al, 2009 ; Octavia et al, 2012 ). The successful use of doxorubicin has been hampered by its toxicity to numerous organs such as the heart (Yilmaz et al, 2006 ; Carvalho et al, 2009 ; Rashid et al, 2013 ; Indu et al, 2014 ; Afsar et al, 2017 ; Bordbar et al, 2019 ; Ikewuchi et al, 2021a ), liver (Carvalho et al, 2009 ; Indu et al, 2014 ; Chen et al, 2016 ; Alghorabi et al, 2019 ; Ikewuchi et al, 2021b ), kidneys (Yilmaz et al, 2006 ; Carvalho et al, 2009 ; Rashid et al, 2013 ; Ren et al, 2016 ; Bordbar et al, 2019 ; Sabapathy et al, 2019 ; Ikewuchi et al, 2021c ), and lungs (Vapa et al, 2012 ; Jagetia and Lalrinpuii, 2018 ). Hepatonephrotoxicity induced by doxorubicin is accompanied by increased plasma levels of creatinine, urea, uric acid, gamma-glutamyl transferase, lactate dehydrogenase, alanine transaminase, aspartate transaminase, and alkaline phosphatase and decreased plasma albumin and total protein levels (Öz and İlhan, 2006 ; Yilmaz et al, 2006 ; Lee et al, 2013 ; Ahmed et al, 2019a ).…”

Protective effect of aqueous leaf extracts of Chromolaena odorata and Tridax procumbens on doxorubicin-induced hepatotoxicity in Wistar rats

“…After zeroing the spectrophotometer with a blank containing 0.2 mL of distilled water in the place of the sample, they were read at 532 nm. The homogenates’ ascorbic acid contents were estimated by iodine titration, as adopted from Ikewuchi et al 60 One milliliter (1.0 mL) of the sample was added to 5 mL of reaction mix (31.746 mg % starch in 1.243% (v/v) HCl); and titrated with iodine solution, until a permanent blue color appeared.…”

Plant Flavonoids on Oxidative Stress-Mediated Kidney Inflammation

“…Further, Dox-induced oxidative stress in renal tissue is characterized by an increased lipid peroxidation marker, malondialdehyde (MDA), and decreased glutathione (GSH) levels. Dox decreases the renal function indicators in urine and serum, including pH, specific gravity, total protein, albumin, urea, creatinine, uric acid, globulin, and blood urea nitrogen (BUN) [ 26 , 27 ]. Frequent use of cisplatin, another chemotherapeutic drug, could also cause nephrotoxicity.…”