Ameliorative Effect of Olea europaea Leaf Extract on Cisplatin-Induced Nephrotoxicity in the Rat Model (original) (raw)
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International Journal of Pharmacy and Pharmaceutical Sciences, 2021
Objective: The main objective of this study is to investigate the antioxidant and nephroprotective efficacy of moringa oleifera seed extract (MOSE) against cisplatin which induced acute renal injury. Methods: Forty male Wister rats were equally segregated into 4 groups (10 rats per group): group I (0.5 ml of sterile saline orally), group II (200 mg MOSE/kg b. wt orally for 10 consecutive days), group III (7.5 mg cisplatin/kg b. wt/intraperitonially as a single dose on the 5 th day of the experiment) and group IV (200 mg moringa oleifera seed extract (MOSE)/kg orally for 10 d followed by 7.5 mg cisplatin/kg body weight/intraperitonially once as a single dose on the 5 th day of the experiment. Serum biochemical analysis of renal biomarkers (urea, uric acid, and creatinine), oxidative stress markers (malondialdehyde [MDA]), a crucial antioxidant enzyme (catalase) and the expression of renal activity interleukin (IL)-6, (IL)-10 and Tumer necrotic factor (TNF-α) mRNA were determined. Histopathological examination of renal tissue was done. Results: Cisplatin induced renal damage, increased renal biomarkers (urea, creatinine and uric acid)(375.87±1.65, 5.238±0.25, 4.47±0.25). Tissue concentrations of malondialdehyde, IL-6 and TNF-α.(387.56±0.97, 2.188±0.20, 3.06±0.27)compared to control group(140.58±1.25,0.938±0.017, 1.24±0.17), (163.99±1.34, 1.008±0.05, 0.982±0.026) Moreover, cisplatin induced significantly down-regulation of anti-inflammatory (IL-10) and catalase (0.780±0.47, 1.62±0.06) compared to control one (1.010±0.02, 3.12±0.11),. The histopathological examination showed renal tissue damage and degeneration of tubules in the cortical portion in cisplatin group. However, interestingly concurrent adminsteration of the MOSE with cisplatin can alleviated the renal damage, oxidative stress and renal toxicity caused by cisplatin. Conclusion: These results suggest that the antioxidant and the anti-inflammatory effects of MOSE alleviate the cisplatin-induced nephrotoxicity.
Food and Chemical Toxicology, 2019
Oleanolic acid (OA) is a natural triterpenoid that possesses numerous beneficial health effects such as antioxidant, antiinflammatory, and anti-apoptotic activities. However, the renoprotective effect of OA in cisplatin (CP)-intoxicated mice is unknown. In this study we investigated the effect of OA on CP-induced nephrotoxicity. Treatment with OA ameliorated the increased serum markers and histological features of kidney injury. Also, CP administration increased renal expression of oxidative stress markers HO-1 and 4-HNE as well as the expression of proinflammatory cytokine TNF-α and NF-κB, which was reduced by OA administration, indicating the inhibition of oxidative stress and inflammation. Likewise, an increased expression of caspase-3/9 with concomitant increase in PARP cleavage suggested CP-induced apoptosis in the kidneys. OA exhibited anti-apoptotic activity by decreasing the expression of stated markers. Treatment with OA also ameliorated LC3B-II and Atg5 expression induced ...
Polish Journal of Food and Nutrition Sciences, 2014
The present study investigated the protective effect of extracts prepared from grape, coriander, roselle and fennel in a rat model of kidney dysfunction induced by intraperitoneal cisplatin. A mixture of ethanol and petroleum ether extracts was prepared from a given plant. Six groups of rats were analyzed; control healthy, cisplatin group and 4 test groups where rats were given a daily oral dose of each extract mixture before cisplatin injection. Different biochemical and cytogenetic parameters and kidney histopathology were determined. Total phenolic contents, fatty acids and unsaponifiable matter (UNSAP) were assessed in the extracts. Results showed roselle ethanol extract to have the highest phenolic content (15.584 g GAE/100 g extract). Fatty acid analysis revealed the presence of linoleic and linolenic acid in all studied plants. Coriander oil showed the highest content of unsaturated fatty acids (85%). GLC investigation of the UNSAP showed the presence of campesterol in all the studied plants. Grape oil contained the highest content of phytosterol (15.9%). Cisplatin treatment induced significant increase in plasma urea, creatinine and malondialdehyde along with significant reduction in plasma albumin, total protein, catalase activity and total antioxidant level as well as reduction in creatinine clearance compared to normal control. Histopathological examination proved the induction of kidney dysfunction by cisplatin. Chromosomal aberration and sperm-shape abnormalities were noticed after cisplatin treatment. Administration of extract mixtures produced improvements in biochemical, histopathological and cytogenetic parameters. Extracts mixture under study offered protection from cisplatin induced kidney dysfunction via antioxidant and possibly anti-inflammatory actions.
Protective effect of pomegranate seed oil against cisplatin-induced nephrotoxicity in rat
Renal Failure, 2015
Clinical use of cisplatin is limited by its nephrotoxicity. Cisplatin-induced nephrotoxicity is associated with an increase in oxidative stress, leading ultimately to kidney dysfunction. The aim of this study was to investigate the effect of pomegranate seed oil against nephrotoxicity induced by cisplatin in adult rats. Animals were divided into four groups. Group I received corn oil (1 mL/kg). Group II received cisplatin (8 mg/kg). Group III and IV received pomegranate seed oil (PSO) 0.4 mL/kg and 0.8 mL/kg one hour before cisplatin injection for 3 days, respectively. Blood samples were collected by cardiac puncture and used for measuring urea and creatinine concentration. Twenty-hour urine samples were collected to measure protein and glucose concentration. The right kidney fixed in formalin for histological examination and the left kidney was homogenized for measurement of malondialdehyde and total sulfhydryl groups. A significant elevation of serum creatinine, urea, urinary gluc...
Bioengineered, 2021
The overuse of cisplatin (>50 mg/m2) is limited to nephrotoxicity, ototoxicity, gastrotoxicity, myelosuppression, and allergic reactions. The objective of this study was to investigate the nephroprotective effects of Daucus carota and Eclipta prostrata extracts on cisplatin-induced nephrotoxicity in Wistar albino rats. The study involved male Wistar albino rats of 8 weeks weighing 220–270 g. A single injection of 5 mg/kg was injected into the rats for nephrotoxicity. Rats were divided into four groups based on dose conentrations. Blood and urine samples of rats were collected on the 0, 7th, 14th, and 21st days for nephrological analysis. The results showed that Cis + DC/Cis + EP (600 mg/kg) significantly (p < 0.001) increased the body weight and reduced the kidney weight of cisplatin-induced nephrotoxicity in rats (p < 0.001) as compared to Cis group. The results showed that 600 mg/kg administration of Cis + DC/Cis +EP successfully (p < 0.005) improved the urine and plasmin creatinine, Na, and K level compared to the Cis group. Histopathological results confirmed that Cis + EP/Cis + DC effectively improved the renal abnormalities. It is concluded that the co-administration of Cis + EP extract showed exceptional nephroprotective effects at a dose rate of 600 mg/kg.
Effect of Methanolic Extract of Corn Silk on Cisplatin-Induced Nephrotoxicity in Rats
PubMed, 2018
Background: Cisplatin is a cytotoxic agent in cancer therapy. Nephrotoxicity is considered as a side effect of cisplatin usage. Using rate models, we studied the possible protective impact of corn-silk (CS) extract against cisplatin-induced nephrotoxicity. Materials and methods: Thirty-five experimental rats were divided into five groups (n=7 per each group) as follow: C1: Control received distilled water only; C2: received one dose of cisplatin, and CS: received 300 mg/kg/day of CS. Both CS1 and CS2 received 200 and 300 mg/kg/day of the CS extract orally, individually, for eight consecutive days. CS1 and CS2 received a single dose of cisplatin on the first day only. The specific biochemical markers and histopathological alterations were evaluated. Result: According to our results, cisplatin administration could have induced severe degeneration in all parts of the nephron tubules and liver. Pre-treatment with CS exhibited a significant decrease in the malondialdehyde (MDA) levels as compared to the values obtained after treatment with cisplatin alone (P<0.01). Moreover, the CS extract with 200 mg dose showed significant (P<0.01) protection against the cisplatin-induced elevation of blood urea nitrogen. Further, the serum levels of alanine transaminase and aspartate transaminase were higher in the cisplatin-treated groups, when compared to the control group (P<0.05). Furthermore, the hepatic function was also improved in cisplatin-treated animals, which were pre-treated with CS. Conclusion: CS has the potential to attenuate nephrotoxicity and lipid peroxidation induced by cisplatin in rats.
The Effects of Cornus mas Hydro-Methanolic Extract on Cisplatin-Induced Nephrotoxicity in Rats
Pharmaceutical Sciences
Introduction Cisplatin (cis-diamminedichloroplatinum II) is one of the most effective and widely used chemotherapeutic agents for treating malignant tumours in testis, ovary, breast, lung, cervix, and many other organs. 1-3 The therapeutic effects of cisplatin are dose-dependent, 4 but cisplatininduced nephrotoxicity is one of the serious adverse effects that limit its clinical utility at high doses. 5-7 After administration of cisplatin, about 34% of patients develop renal dysfunction followed by acute kidney injury, which is associated with high morbidity and mortality. 3,8 The mechanism underlying cisplatin-induced nephrotoxicity is complex and not fully clear. The renal dysfunction is involved in mitochondrial oxidative stress, inflammation, and tubular necrosis. 5,9-11 It is well known that medicinal plants can be seen as a main source of new chemical substances with potential therapeutic effects and there has been a shift towards the therapeutic evaluation of herbal products in recent years. Cornelian cherry (Cornus mas L.), a medicinal plant, is a member of the Cornaceae species. 12,13 The plant is found in parts of central and southern Europe as well as in western Asia, including the northern forests of Iran (East Azerbaijan and Qazvin provinces). 13,14 It is a small tree or medium-to-large deciduous shrub that grows up to 5-12 m. 13 Cornelian cherries are typically single-seeded, oliveshaped red fruits. They are sweet-sour and 10-23 mm long. The fruits may be consumed fresh or used to produce jam, stewed fruit, compote, or syrup. The fruits are rich in sugar, organic acids, oxalic acid, tannins, anthocyanins (delphinidin-3-glucoside, cyanidin-3rhamnoglucoside, cyanidin-3-glucoside, cyanidin-3galactoside, and pelargonidin-3-galactoside), phenols, flavonoids, and other antioxidants. Fresh cornelian cherry fruits contain B1, B2, E vitamins, folic acid, and twice as much vitamin C than oranges. Cornelian cherries have high contents of K and Mg, and low contents of Na, Cu, Mn, Fe, and Zn; their levels of toxic elements are negligible. 12-16 The cornelian cherry fruits have been used for treating sore throat, digestion problems, diarrhoea, A B S T R A C T Background: Cisplatin (Cis) is a chemotherapeutic agent and nephrotoxicity is a serious adverse effect of the drug. This study investigated the protective effects of Cornus mas fruit hydro-methanolic extract (CME) on cisplatin-induced nephrotoxicity in a rat model. Methods: Forty Wistar rats were divided into the control group, CME group, CME 300 + Cis group, CME 700 + Cis group, and Cis group. After the intervention samples were taken for biochemical and histopathological analysis. Results: The CME analysis showed considerable total antioxidant and total phenol contents. The blood serum urea and creatinine increased (p < 0.01) in the Cis group rats. In the Cis + CME groups, the parameters were not significantly different from that of the control group. There were no significant differences in the renal activities of SOD, GPx, CAT, and TAC between the Cis-treated and control groups (p > 0.05). The renal MDA levels of the Cis and CME 300 + Cis groups decreased significantly in comparison to the control and the CME groups (p < 0.01 and p < 0.05, respectively). In the histopathological examination, mild to severe degeneration was observed in the Cis group. Despite the presence of mild degeneration, they were less severe in the Cis + CME groups, and maintained a better morphology when compared to the Cis group (p < 0.01). Conclusion: The results showed renoprotective effects of CME against Cis-induced nephrotoxicity in rats.
Frontiers in Pharmacology, 2023
Herein, we explored the protective effect of Leonotis ocymifolia (Burm.f.) Iwarsson aerial parts extract (LO) against cisplatin (CP)-induced nephrotoxicity in rats and profiled their phytocontents. A total of 31 compounds belonging to organic and phenolic acids and their glycosides as well as flavonoids and their Oand C-glycosides were identified through LC-MS/MS. The DPPH and FRAP assays revealed that the extract had powerful antioxidant properties. The in vivo results demonstrated that administering LO extract for 30 days (40 and 80 mg/kg b. w.) significantly improved the altered renal injury markers via reducing creatinine (high dose only) and uric acid levels compared to the Cp-group. The deleterious action of cisplatin on renal oxidative stress markers (GSH, MDA, SOD, and CAT) were also mitigated by LO-pretreatment. The reduction of the inflammatory marker (IL-6), and inhibition of DNA fragmentation, highlighted the prophylactic action of LO in kidney tissue. Molecular docking followed by a 100 ns molecular dynamic simulation analyses revealed that, amongst the 31 identified compounds in LO, chlorogenic and caffeoylmalic acids had the most stable binding to IL-6. The nephroprotective effects were further confirmed by histopathological observations, which showed improvement in ultrastructural changes induced by cisplatin. The observed findings reinforce the conclusion that L. ocymifolia extract exerts nephroprotective properties, which could be related to its antioxidant and anti-inflammatory activities. Further studies are required to determine the therapeutic doses and the proper administration time.
Cytotechnology, 2014
Cisplatin (CP) is a chemotherapeutic drug used in treatment of malignancies. However, its clinical utility is limited by nephrotoxicity. The purpose of the present study was to investigate the protective role of grape seed proanthocyanidin extract (GSPE) (100 mg/kg/day) or fish oil (FO) (5 ml/kg/ day) against cisplatin induced nephrotoxicity in terms of biochemical parameters, oxidative stress and DNA damage. CP nephrotoxiciy is manifested by increased levels of serum creatinine, urea and uric acid, accompanied by their decrease in urine. Na, K and Ca levels were altered in both serum and urine. In addition, cisplatin caused a decrease in renal GSH, SH-group, SOD, GST, and Na-K-ATPase levels. However the levels of MDA, H 2 O 2 and NO were increased. Also, we assessed the renal genotoxic potential of cisplatin as manifested by an increase in the tail length of DNA, tail intensity (DNA %) and tail moment. On the other hand, administration of GSPE or FO pre-cisplatin treatment ameliorated the current changes in most of the above tested parameters, particularly oxidative stress, endogenous antioxidant defense system and DNA damage indicating their curative effect. Thus, it can be concluded that the consumption of GSPE or FO might be useful for preventing nephrotoxicity caused by cisplatin treatment.