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Diclofenac medication has been extensively used for anti-inflammatory, anti-pyretic, and analgesic actions. Its abiding usage and overdose have induced toxicity and harmful effects on the liver, kidney, and gastrointestinal tract. The research aims to scrutinize the protective effect of Madhuca longifolia seed oil against diclofenac-induced toxicity in female Wistar albino rats. A period of 10 days of study was aimed at 7 groups; Group 1 was assigned as normal control. Group 2 has been administered diclofenac (50 mg/kg b.w. /day, i.p.) only on the last two days of each study period. Group 3 and Group 4 have been pre-treated with 1 mL, and 2 mL of Madhuca longifolia seed oil, respectively, and diclofenac was induced as per Group 2. Group 5 was treated with the standard drug silymarin and diclofenac. Group 6 and Group 7 were given 1 mL and 2 mL of Madhuca longifolia seed oil alone. After the study period, parameters like liver enzyme markers, renal enzyme markers, and antioxidants were measured, and tissue samples were analyzed for histopathological changes. The results proved that pre-treatment of 1 mL of Madhuca longifolia seed oil has efficacy against diclofenac-induced toxicity.
ABSTRACT
Diclofenac medication has been extensively used for anti-inflammatory, anti-pyretic, and analgesic actions. Its abiding usage and overdose have induced toxicity and harmful effects on the liver, kidney, and gastrointestinal tract. The research aims to scrutinize the protective effect of Madhuca longifolia seed oil against diclofenac-induced toxicity in female Wistar albino rats. A period of 10 days of study was aimed at 7 groups; Group 1 was assigned as normal control. Group 2 has been administered diclofenac (50 mg/kg b.w. /day, i.p.) only on the last two days of each study period. Group 3 and Group 4 have been pre-treated with 1 mL, and 2 mL of Madhuca longifolia seed oil, respectively, and diclofenac was induced as per Group 2. Group 5 was treated with the standard drug silymarin and diclofenac. Group 6 and Group 7 were given 1 mL and 2 mL of Madhuca longifolia seed oil alone. After the study period, parameters like liver enzyme markers, renal enzyme markers, and antioxidants were measured, and tissue samples were analyzed for histopathological changes. The results proved that pre-treatment of 1 mL of Madhuca longifolia seed oil has efficacy against diclofenac-induced toxicity.
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PD-1/PD-L1 (programmed cell death 1/programmed cell death 1 ligand 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) are currently approved major immune checkpoints. Immune checkpoint inhibitors against them are novel monoclonal antibodies that perform well in a variety of malignancies such as melanoma, renal cell carcinoma, non-small-cell lung cancer, urothelial carcinoma and Hodgkin′s lymphoma. However, with the increasing use of immune checkpoint inhibitors, immune-related adverse events cannot be ignored. The incidence of gastrointestinal toxicity is second only to skin toxicity. In this review, we focused on the mechanisms of these immune checkpoint inhibitors and the characteristics of gastrointestinal toxicity induced by them, and also discussed the clinical management strategies.
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PD-1 / PD-L1 (programmed cell death 1 / programmed cell death 1 ligand 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) are currently approved major immune checkpoints. Immune checkpoint inhibitors against them are novel monoclonal antibodies that perform well in a variety of malignancies such as melanoma, renal cell carcinoma, non-small-cell lung cancer, urothelial carcinoma and Hodgkin's lympho-ma. However, with the increasing use of immune checkpoint inhibitors, immune-related adverse events can-not be ignored. The incidence of gastrointestinal toxicity is second only to skin toxicity. In this review, we focused on the mechanisms of these immune checkpoint inhibitors and the characteristics of gastrointestinal toxicity induced by them, and also discussed the clinical management strategies.
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To study the effects of different fraction of Euphorbiae Pekinensis Radix before and after processing with vinegar on liver and gastrointestinal toxicity of zebrafish embryos,the zebrafish embryos after fertilized 12 h(12 hpf) were exposed to different concentrations of solution until 96 h(96 hpf),for observation of the toxicity response of the liver and gastrointestinal of individual zebrafish embryos. The results showed that toxicity increased in a dose-dependent manner. The liver and gastrointestinal toxicity of the zebrafish embryos in various polar fractions of Euphorbiae Pekinensis Radix before and after processing with vinegar was mainly manifested as slow liver development,smaller liver area,edema of yolk sac,delayed absorption,slowing of gastrointestinal motility,abnormal function of gastrointestinal goblet cell secretion. In addition,the toxicity of different polarity was followed by petroleum ether,dichloromethane,ethyl acetate. The above results indicated that the toxicity was reduced after processing with vinegar,and the fractions of petroleum ether and methylene chloride were the main sites responsible for liver and gastrointestinal toxicity.
Subject(s)
Animals , Acetic Acid , Drugs, Chinese Herbal , Liver , Plant Roots , ZebrafishABSTRACT
Objective To make a preliminary investigation on the mechanism of the glycyrrhizin flavonoids alleviating the gastrointestinal toxicities of irinotecan. The pharmacological effects of glycyrrhizin flavonoids on the changes of endogenous differential metabolites of irinotecan-induced gastrointestinal toxicities were evaluated by using GC-MS metabolomics methods. Methods C57BL/6 mice were divided into normal group, model group, positive group (ciprofloxacin), and glycyrrhizin flavonoids group. Irinotecan induced colitis model were established in mice by intraperitoneally injected. The body weight, length of colon, and tissue sections were used to evaluate the effect of glycyrrhizin flavonoids on alleviating irinotecan-induced experimental colitis. Meanwhile, to evaluate the attenuating effect of glycyrrhizin flavonoids from the perspective of metabonomics, GC-MS was used for non-targeted metabolism in order to find out the the change of related metabolites in plasma between experimental colitis mice and glycyrrhizin flavonoids treatment mice. Furthermore, metabolic pathway was constructed by MetaboAnalyst software to explore the potential mechanism. Results Glycyrrhizin flavonoids could significantly reduce the loss of body weight, colon shortening, and intestinal damage caused by irinotecan administration, and effectively reverse the irinotecan-induced plasma metabolic disorders in mice, including fatty acid metabolism, amino acid metabolism and carbohydrate metabolism, significantly callback seven long-chain fatty acids such as lauric acid, palmitic acid, linoleic acid, oleic acid, linolenic acid, palmitic acid monoglyceride, and oleic acid monoglyceride. Conclusion Glycyrrhizin flavonoids could improve the irinotecan-induced experimental colitis in mice by regulating linoleic acid metabolism and alpha-linolenic acid metabolism.
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OBJECTIVE: This study was performed to assess the cost-effectiveness of cyclooxygenase-2 (COX2)-selective inhibitor, non-selective non-steroidal anti-inflammatory drugs (NSAIDs), and non-selective NSAID with proton pump inhibitors (PPIs) while considering upper and lower gastrointestinal (GI) safety in patients with rheumatoid arthritis (RA). METHODS: A Markov model was used to estimate the costs and effectiveness. Estimates of therapeutic efficacy and upper/lower GI safety were based on results from large randomized controlled trials. The main outcome measure was cost effectiveness, based on the quality-adjusted life years (QALYs) gained. Safety parameters included clinical upper GI symptoms, uncomplicated ulcer, upper GI bleeding, upper GI perforation, clinical lower GI symptoms, lower GI bleeding, and lower GI perforation. Cost data were obtained from patients treated in a tertiary referral center in Korea. RESULTS: The expected three year cost was 3,052,800 Korean won (KRW) for COX2-selective inhibitor, 3,170,800 KRW for nonselective NSAID, and 3,325,900 KRW for non-selective NSAID with PPI. QALYs were 2.87446, 2.85320, and 2.85815, respectively. The total cost for COX2-selective inhibitor use was lower than non-selective NSAID, but QALY was higher, indicating that the incremental cost effectiveness ratio of COX2-selective inhibitor is superior. CONCLUSION: COX2-selective inhibitor has reasonable cost-effectiveness adjusted for upper and lower GI toxicity for patients with RA in Korea.
Subject(s)
Humans , Arthritis, Rheumatoid , Cost-Benefit Analysis , Cyclooxygenase 2 , Hemorrhage , Korea , Outcome Assessment, Health Care , Proton Pump Inhibitors , Quality-Adjusted Life Years , Tertiary Care Centers , UlcerABSTRACT
Non-steroidal anti-inflammatory drugs (NSAIDs) have been successfully used for the alleviation of pain and inflammation in the past and continue to be used daily by millions of patients worldwide. However, gastrointestinal (GI) toxicity associated with NSAIDs is an important medical and socioeconomic problem. Local generation of various reactive oxygen species plays a significant role in the formation of gastric ulceration associated with NSAIDs therapy. Co-medication of antioxidants along with NSAIDs has been found to be beneficial in the prevention of GI injury. This paper describes the synthesis and biological evaluation of N-1-(phenylsulfonyl)-2-methylamino-substituted-1H-benzimidazole derivatives as anti-inflammatory analgesic agents with lower GI toxicity. Studies in vitro and in vivo demonstrated that the antioxidant activity of the test compounds decreased GI toxicity.
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Objective To identify dosimetric predictors for the development of gastrointestinal toxicity in patients with pancreatic adenocarcinoma treated with TOMO radiotherapy .Methods From January 2014 to Janu-ary 2015 ,we analysed the medical records of 68 pancreatic cancer patients who received helical tomotherapy from Air Force General Hospital .The stomach and duodenum were contoured separately to determine their dose volume histogram(DVH)parameters.Chi-square test was employed to analyze the count data .Spearman correlation anal-ysis was used to analyze the relationship between occurrence of gastrointestinal toxicity and clinical and physical factors.Logistic regression models was performed to identify risk factors associated with gastrointestinal toxicity . Results The median follow-up was 9 months(4~16 months).18 patients experienced grade II acute gastroin-testinal toxicity ,1 patient experienced grade Ⅲ acute gastrointestinal toxicity , whereas 17 patients experienced grade II late gastrointestinal toxicity ,1 patient experienced grade Ⅲlate gastrointestinal toxicity .On UVA,the vol-ume,Dmean,D1,D3,D5,D10,V5 to V40,and V5′to V45′of duodenum were significantly associated with GradeⅡor higher gastrointestinal toxicity ( P <0.05 ) .The MVA, V45′of duodenum was independent predictor for gradeⅡor higher gastrointestinal toxicity(P<0.05).The ROC analysis also showed that V45′of 0.5cm3 was the optimal threshold to predict for gastrointestinal toxicity for the entire cohort .Conclusion V45′of duodenum is of greater importance in the judgment of occurrence of hypofractioned radiation -induced gastrointestinal toxici-ty.
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Mycophenolate mofetil (MMF) is a commonly used immunosuppressive drug in the management of transplant recipients. Gastrointestinal (GI) toxicity (diarrhea) is the most frequently reported adverse event in MMF-treated transplant patients. MMF-induced Graft versus Host Disease has rarely been reported in literature. We report a case of MMF-induced colitis with Graft versus Host Disease-like features, to highlight the importance of high clinical suspicion for its diagnosis, and that appropriate management in such a setting can reduce morbidity and mortality. We also review the relevant literature.