The nephrotoxicity induced by methotrexate is a severe condition that greatly affects its therapeutic potential and has a significant inflammatory component. Fimasartan is an angiotensin receptor blocker that offers organ-protective effects and may be useful in mitigating renal injury. The present study explored the anti-inflammatory potential of two doses of fimasartan against methotrexate-mediated nephrotoxicity. Albino rats were intraperitoneally administered a single methotrexate (20 mg/kg). Intraperitoneal treatment with fimasartan (5 or 10 mg/kg/day) was initiated on day two after methotrexate injection and continued for seven consecutive days. Methotrexate significantly increased serum urea, creatinine, and NGAL concentrations. It also substantially elevates the proinflammatory cytokines (namely, tumour necrosis factor-alpha, interleukin-1 beta, and interleukin-6) levels while reducing renal tissue’s immunomodulatory (interleukin-10) levels. Treatment with both doses of fimasartan significantly restored renal function parameters, lowered the renal concentration of proinflammatory cytokines, and upregulated the renal concentration of the anti-inflammatory mediator interleukin-10. The high fimasartan dose resulted in more pronounced effects on the inflammatory parameters. The obtained data suggested that fimasartan effectively mitigates methotrexate-induced nephrotoxicity by inhibiting inflammation in renal tissue in a dose-dependent manner.
Drug-induced acute kidney injury is a serious disorder. Oxidative stress has a key role in its initiation and progression. In this study, the possible ameliorative effect of fimasartan against methotrexate-induced nephrotoxicity was investigated in comparison with α-tocopherol in rats. Wistar rats were allocated into six groups and treated as follows: group Ӏ received water on a daily basis for 8 successive days; group ӀӀ received methotrexate (20 mg/kg) on day 1, followed by water for 7 successive days; group ӀӀӀ received fimasartan (3 mg/kg/day) for 7 successive days; group IV received α-tocopherol (1 g/kg/day) for 7 successive days; group V re
... Show MoreAngiotensin receptor blockers are well known for their therapeutic efficacy and fimasartan has been used safely and efficiently since 2010 in the treatment of hypertension. The study aimed to examine the anti-inflammatory effect of fimasartan in egg albumin-induced inflammation in rats. Rats were treated with diclofenac (25 mg/kg, intraperitoneally) or fimasartan at two different doses (3 or 10 mg/kg, intraperitoneally). The increase in the thickness of the paw was considered to be edema, which was measured using a vernier caliper. Serum was collected to analyze the systemic production of the inflammatory mediators TNF-α, and IL-6. The results showed that fimasartan in both doses significantly reduced edema in inflamed rat paws and produce
... Show MoreAbstract
Nephrotoxicity is defined as rapid deterioration in kidney functions. It arises from direct exposure to drugs or their metabolites. Methotrexate is a famous chemotherapeutic drug with anti-inflammatory and immunosuppressive properties. A high-dose methotrexate-induced renal dysfunction can be life threatening. Cyanocobalamin, one of the forms of vitamin B12, acts as a coenzyme in the conversion of homocysteine to methionine in the cytosol, and the conversion of methylmalonyl-CoA to succinyl-CoA in the mitochondrion. This study is designed to examine the effect of cyanocobalamin in two different doses each co-administered with methotrexate at 20 mg/kg induced nephrotoxicity in rat
... Show MoreBoth methotrexate and vitamin D3 are used in combination for the treatment of various diseases. The aim of this study is to highlight the effect of vitamin D3 on methotrexate-induced jejunum damage using biochemical and histopathological studies. Seven groups of both sexes of rats were selected and treated as follows: (Group I and Group II) : control 1,control 2 (I.P normal saline) daily for 14 and 21 days respectively ; (Group III and Group IV) :vitamin D3 groups (500 IU/rat/day) orally for 14 and 21 days, respectively;(Group V): once daily dose of methotrexate 20mg/kg, I.P injected for 4 days;(Group VI):vitamin D3 (500 IU/rat/day) once daily for 14 days and methotrexate (20 mg/kg I.P) injected only at day 10;.(Group
... Show MoreThe liver protective effects of pentoxifylline were studied through pre-treatment of rats with various intraperitoneal (IP) doses (25, 50 and 100mg/kg/day) 14 days before induction of liver toxicity by carbon tetrachloride (CCl4). The parameters of oxidative stress, malondialdehyde (MDA) and reduced glutathione (GSH) were measured in liver homogenate in addition to histopathological examinations. Analysis of data revealed significant amelioration of oxidative stress in groups of animals pre-treated with different doses of pentoxifylline (PTX) compared to group of animals intoxicated by CCl4 as evidenced by lowering MDA contents and elevation of GSH levels in liver tissue homogenate but the levels still signifi
... Show MoreCyclophosphamide is chemotherapeutic agent that utilized for the treatment of different malignancies; however its’ used associated with numerous adverse effects. Vitamin B2 and vitamin B12 suggested having myeloprotective effect. This work is designed to investigate the myeloprotective effect of both vitamins against cyclophosphamide induced myelosuppression. One hundred adult rats of both sexes were used in this study. The animals were randomly enrolled into ten groups of 10 rats each. Group I: Control group. Group II: Cyclophosphamide-treated. Group III and Group IV Orally-administered vitamin B2 (10, and 40 mg/kg/day), respectively alone for 7 days. Group V:
... Show MoreMethotrexate (MTX) is widely used chemotherapeutic agent with different side effects including germ cells toxicities. Silibinin is one of the structural isomers of silymarin, with different phytotherapeutic applications, and its possible protective effects against MTX induced germ cells damage were investigated in this work. Twenty five male mice were divided into five groups (n=5) allocated as follows: Group 1 received buffer for five days given by single intraperitoneal (IP) injection per day; Group 2 in addition to buffer for five days, animals received at day five single dose of 20mg/kg of MTX IP. Groups (3, 4, and 5) received respectively, (50, 100, or 150mg/kg body weight) of silibinin IP single daily dose for five days then at day fi
... Show MoreMethotrexate (MTX), a folic acid antagonist is widely used for the treatment of a variety of tumors. In the present study, the possible protective effect of aqueous green tea extract (AGTE) in methotrexate-induced haematotoxicity was investigated.Four main groups of white Albino rats were used: control group, (MTX) group, following a single dose of MTX (20 mg/kg, i.p.) saline was administered for 5 days. (AGTE) group, was treated with 1.25% concentration of AGTE only for 12 days and the (MTX+AGTE) group, in thism group rats received different concentrations of AGTE (0.625, 1.25 and 2.5%), as their sole source of drinking water, 7days before and 5 days after MTX treatment. MTX induced significant decreases in RBC, Hb, Hct, WBC and pl
... Show MoreCurrent study aimed to investigate the effect of piroxicam on some hematological
and biochemcal parameters. For this reason forty males mature Sprage Dawlley rats
were divided into four equal groups. control group administrated distilled water
(G1), and three groups administrated (20mg/kg,30mg/kg,40mg/kg) body weight of
piroxicam for 45 days. The results showed significant decrease (P<0.05) in
hemoglobin (Hb) and packed ceq volume (PCV) in groups treated with
(30,40)mg/kg of piroxicam, while the treated groups produced significant increease
(P<0.05) in the total white blood cell count (WBC). On the serum biochemical
porameters, Piroxicam caused increase in the level of liver enzyme amunotans ferase
(ALT)