Retrospective Observational Study to Evaluate Causality, Preventability and Severity of Adverse Drug Reaction Associated with Anticancer Drugs in a Tertiary Care Hospital in Northern India.

BACKGROUND: Chemotherapy has high efficacy, but it is associated with several adverse drug reactions (ADRs). OBJECTIVES: A retrospective observational study to explore the prevalence, causality, and preventability of ADRs of anticancer agents was conducted. METHODS: The study was carried out at Punjab Institute of Medical Sciences Jalandhar, Punjab after obtaining IEC approval. The data was collected from cancer patients undergoing treatment at the hospital. The causality assessment of the collected data was done by using WHO causality assessment criteria. The preventability and severity of the reported ADRs were also assessed. RESULTS: From 50 medical records, a total of 47 ADRs were recorded among 25 patients, out of which 16 were females and the rest were males. The cancer cases observed were breast carcinoma, leukaemia, lung, colon, and ovarian cancer. The highest number of ADRs were observed with alkylating agents, followed by taxanes, antimetabolites, kinase inhibitors, and monoclonal antibodies. The most affected organ systems were the gastrointestinal system, blood, and lymphatic system. According to the causality assessment, the majority of the ADRs were of the "possible" category. Preventability analysis showed that 85.11% of ADRs were unavoidable reactions, while 14.89% of ADRs were possibly avoidable. Severity analysis of ADRs showed that 87.23% of ADRs were mild and 12.77% were of moderate severity. The majority of the ADRs were unavoidable and mild to moderate in severity. CONCLUSION: Since the majority of the ADRs were of the unavoidable category, it indicates that the treatment regimens are acceptable as per the current clinical management of cancer patients.

Augmentation of hepatoprotective potential of Aegle marmelos in combination with piperine in carbon tetrachloride model in wistar rats.

The current study investigated hepatoprotective and antioxidant effects of Aegle marmelos leaves extract. The major constituent present in the extract i.e. rutin was quantified by using HPLC. Further, the study explored hepatoprotective effect of A. marmelos (70% ethanol extract) in combination with piperine. The normal control and carbon tetrachloride (CCl4) administered rats were divided into 7 groups. Hepatic damage biomarkers were determined in serum samples and oxidative stress biomarkers (malondialdehyde, reduced glutathione, glutathione reductase, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase), pro-inflammatory and anti-inflammatory cytokines were determined in liver homogenates. CCl4 caused marked liver damage as evident by significant increased activities of serum alkaline phosphatase, bilirubin, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, Interleukin 10 and Tumor necrosis factor-α levels compared to normal control. The oxidative stress parameters also significantly modulated in CCl4 group as compared to normal control. Treatment with A. marmelos reduced the severity of toxicity in a dose dependent fashion and the results of A. marmelos extract 50 mg/kg group were comparable to silymarin group. The low dose of A. marmelos extract (25 mg/kg) per se did not significantly reversed the hepatotoxicity but low dose of A. marmelos in combination with piperine showed significant reversal of hepatotoxicity. In conclusion, A. marmelos exerts potential hepatoprotective activity through its antioxidant and anti-inflammatory properties which was enhanced by co-treatment with piperine.

Hepatoprotective effect of Aegle marmelos augmented with piperine co-administration in paracetamol model

ABSTRACT The current study explored hepatoprotective effect of Aegle marmelos (L.) Corrêa, Rutaceae, leaves extract. Potentiation of A. marmelos hepatoprotective effect with piperine co-administration was also explored. Wistar rats were randomly divided into seven groups: (i) normal control, (ii) paracetamol group, (iii) silymarin group, (iv) extract-25 group (25 mg/kg body), (v) extract-50 group: (50 mg/kg), (vi) extract-100 group (100 mg/kg) and (vii) extract-25 + piperine group. Hepatotoxicity was induced by administering paracetamol orally in a dose of 400 mg/kg for seven days. The drugs were administered 30 min prior to paracetamol administration and continued for seven days. Animals were 'sacrificed' at the end of treatment and serum was collected for evaluating alkaline phosphatase, bilirubin, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase IL-10 and TNF-α levels. Liver homogenates were used for determination of oxidative stress (malondialdehyde, reduced glutathione, superoxide dismutase, catalase, glutathione reductase, GSH-S-transferase, glutathione peroxidase and glucose-6-phosphate dehydrogenase). Serum biochemical markers were significantly higher in paracetamol group as compared to normal control group. Significant increase in oxidative stress parameters and inflammatory mediators was also observed. Treatment with A. marmelos curtailed the toxic effects of paracetamol in a dose dependent fashion. 100 mg/kg dose of A. marmelos was found to be most hepatoprotective. The results of extract-100 group were comparable to silymarin group. Low dose of A. marmelos i.e., 25 mg/kg was combined with piperine to evaluate potentiation of hepatoprotective effects of A. marmelos. Piperine co-administration potentiated the hepatoprotective effects, because the combination group results were comparable to high dose A. marmelos group. A. marmelos exerts hepatoprotective activity through its antioxidant and anti-inflammatory properties which was enhanced by piperine.

The novel role of ß-aescin in attenuating CCl4-induced hepatotoxicity in rats.

CONTEXT: ß-Aescin has anti-inflammatory, anti-oxidant and antiedematous properties. OBJECTIVE: The present study investigated the hepatoprotective effect and underlying mechanisms of ß-aescin in CCl4-induced liver damage. MATERIALS AND METHODS: Thirty-five Wistar rats were divided into six groups: normal control, CCl4 control, silymarin (50 mg/kg, p.o) and ß-aescin (0.9, 1.8 and 3.6 mg/kg, i.p.) treatment for 14 d. CCl4 (1 mL/kg, i.p. for 3 d) was administered to produce hepatic damage. Ponderal changes and liver marker enzymes were estimated. Hepatic oxidative and nitrosative stress was estimated by levels of thiobarbituric acid reactive substances (TBARS), glutathione (GSH) and nitrite/nitrate. Serum TGF-ß1 and TNF-α were estimated by ELISA technique. Hepatic collagen and histopathological studies were carried out. RESULTS: ß-Aescin (3.6 mg/kg) markedly decreased CCl4-induced increased levels of ALT, AST, ALP (71.77 versus 206.7, 71.39 versus 171.82, 121.20 versus 259 IU/L, respectively), total bilirubin (0.41 versus 1.35 mg/dL), TBARS (2.0 versus 8.83 nmol MDA/mg protein), nitrite/nitrate (352.50 versus 745.15 µg/mL) and increased CCl4-induced decreased GSH levels (0.095 versus 0.048 µmol/mg protein). ß-Aescin (3.6 mg/kg) induced focal regenerative changes in liver and markedly decreased TBARS (2.0 versus 8.83 nmol MDA/mg protein), nitrite/nitrate (352.50 versus 745.15 µg/mL), TGF-ß1 (92.28 versus 152.1 pg/mL), collagen content (110.75 versus 301.74 µmol/100 mg tissue) and TNF-α (92.82 versus 170.56 pg/mL) when compared with CCl4 control. DISCUSSION AND CONCLUSION: The findings suggest that ß-aescin has a protective effect on CCl4-induced liver injury, exhibited via its anti-inflammatory, antioxidative, antinitrosative and antifibrotic properties inducing repair regeneration of liver. Hence, it can be used as a promising hepatoprotective agent.

Protective effect of Mimosa pudica L. in an L-arginine model of acute necrotising pancreatitis in rats.

Mimosa pudica is used in traditional medicine for treating various disorders such as inflammatory conditions, diarrhoea, insomnia, alopecia, urogenital infections and wounds. The present study investigated the effect of M. pudica extract (MPE) on L-arginine-induced acute necrotising pancreatitis in rats. The ethanolic extract of M. pudica leaves was studied for the presence of quercetin and gallic acid using high-performance liquid chromatography. Four groups were employed-normal control rats, L-arginine control rats (two intraperitoneal [i.p.] injections of 2 g/kg at an interval of 1 h), MPE-treated rats (400 mg/kg orally) and melatonin-treated rats (positive control 10 mg/kg i.p.), which were further divided into subgroups according to time points (24 h, 3 days and 14 days). Serum amylase, lipase, tumour necrosis factor-α (TNF-α), pancreatic amylase, nucleic acid content, protein, transforming growth factor-ß1 (TGF-ß1), thiobarbituric reactive substances, glutathione, nitrite/nitrate, collagen content and histopathological examination were carried out. MPE significantly improved acute necrotising pancreatitis by modulating diagnostic markers of pancreatitis such as serum lipase and pancreatic amylase, inflammation (TNF-α), and oxidative and nitrosative stress. Moreover, MPE administration induced regenerative changes in the pancreas evidenced by increased levels of pancreatic proteins, nucleic acid content and histopathology report. In addition, MPE improved TGF-ß1 and collagen levels thereby preventing fibrosis. The current investigation indicates the novel role of MPE in reducing the severity of acute necrotising pancreatitis by plausible mechanisms such as anti-inflammatory and anti-fibrotic activity and by promoting repair and regeneration of the pancreas.