Do Breast Cancer Risk Factors Affect the Survival of Breast Cancer Patients in Southern Sri Lanka?

Background: Breast cancer continues to be a major cause of morbidity among women in Sri Lanka. Possible effects of etiological risk factors on breast cancer specific survival (BCSS) of the disease is not clear.This study was designed to explore the impact of breast cancer risk factors on the BCSS of patients in Southern Sri Lanka. Method: This retro-prospective study included all breast cancer patients who had sought immunohistochemistry services at our unit from May 2006 to December 2012. A pre-tested, interviewer-administered questionnaire was used to gather information on risk factors. BCSS was estimated using the Kaplan-Meier model. Univariate Cox-regression analysis was performed with 95% confidence intervals using the SPSS statistical package. Results: A total of 944 breast cancer patients were included. Five year BCSS was 78.8%. There was a statistically significant difference between the patients who had a family history of breast cancer and no family history of any cancer in terms of the presence/absence of lymph node metastasis (p=0.011) and pathological stage (p=0.042). The majority of the premenopausal patients had associated DCIS (p<0.001) and large tumours (p=0.015) with positive lymph nodes (p=0.016). There was no statistically significant association between hormone receptor subtypes and hormone related risk factors. Univariate analysis revealed that breast cancer risk factors had no significant effect on the BCSS. Conclusion: Even though family history of breast cancer and premenopausal status are associated with poor prognostic features, they, in line with the other breast cancer risk factors, appear to have no significant effect on the BCSS of patients in Southern Sri Lanka.

Effect of Asparagus falcatus on acetaminophen toxicity in mice: a comparison of antioxidative effect with N-acetyl cysteine.

OBJECTIVE: In this study, the effect of Asparagus falcatus extract on acetaminophen-induced liver injury was investigated in vivo. METHOD: Six arms of study. ICR mice (n = 20) were treated with acetaminophen at a single dose of 300 mg/kg (in saline, after a 16-hr fast) to induce hepatotoxicity. Drug control group and pre- and posttreated groups were administered 0.9 g/kg of Asparagus falcatus orally. Serum ALT, AST, ALP, liver GSH, antioxidant enzymes, GPx (glutathione peroxidase), GR (glutathione reductase), GST (glutathione-S-transferase), and liver/serum malondialdehyde (MDA) concentrations were estimated. Liver damage was also assessed histopathologically. The effect of the plant extract was compared with N-acetyl cysteine. RESULTS: Acetaminophen produced liver damage, as manifested by a significant rise (P <. 001, one-way ANOVA) in serum ALT, AST, and ALP, and a reduction (P <. 001) in the liver reduced glutathione (GSH) as compared to respective controls. All enzyme activities and liver GSH were significantly improved in Asparagus-treated mice, with pretreatment providing better results than posttreatment (P <. 05). Histopathologically, mice pretreated with Asparagus showed no liver necrosis. A significant improvement was observed in antioxidant enzyme activities of GPx, GR, and GST in the Asparagus pretreated group (P <. 05). Mice posttreated with Asparagus showed a significant reduction in MDA formation (P <. 05). CONCLUSION: These results suggest that the feeding regimen with Asparagus extract inhibited the progression of hepatic injury induced by acetaminophen.

Hepatoprotective effect of Epaltes divaricata extract on carbon tetrachloride induced hepatotoxicity in mice.

BACKGROUND & OBJECTIVES: Epaltes divaricata is widely used in Sri Lanka as an Ayurvedic medicine. In the present study the hepatoprotective and antioxidative effects of an aqueous extract of E. divaricata plant (Family-Compositae) were investigated against carbon tetrachloride induced hepatocellular injury in mice. METHODS: Healthy male mice (30-35 g body weight, 6-8 wk old) were used. A single dose of carbon tetrachloride (CCl4, 0.5 ml/kg in olive oil) was administered ip to induce hepatotoxicity and the plant extract at a dose of 0.9 g/kg was administered orally by gavage. Animals were sacrificed 24 h and 4 days after the administration of CCl4. Blood and liver tissue were collected for the assessment of serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and liver reduced glutathione level. The liver tissue was used for histopathological assessment of liver damage. RESULTS: Pre-treatment of mice with the plant extract of Epaltes (0.9 g/kg) orally for 7 days significantly reduced serum levels of ALT (P<0.01), AST (P<0.01) and ALP (P<0.001) enzymes by 21.40, 47.36 and 71.12 per cent respectively and significantly increased (P<0.001) the liver reduced glutathione level by 42.32 per cent, 24 h after the administration of carbon tetrachloride. A marked improvement in the enzyme activities and the liver reduced glutathione level was observed in the Epaltes pre-treated mice 4 days after the administration of carbon tetrachloride. Histopathological studies provided supportive evidence for the biochemical analysis. INTERPRETATION & CONCLUSION: The results of the present study indicated that under the present experimental conditions, aqueous extract of Epaltes divaricata showed hepatoprotective abilities against carbon tetrachloride induced liver damage in mice.

Protective effect of Asteracantha longifolia extract in mouse liver injury induced by carbon tetrachloride and paracetamol.

This study was conducted to investigate the protective effect of Asteracantha longifolia Linn (Acanthaceae) plant extract on carbon tetrachloride (CCl4)- and paracetamol-induced acute hepatotoxicity in mice. Hepatotoxicity was induced by the administration of a single intraperitoneal dose of CCl4 (0.5 mL kg(-1) CCl4 in olive oil) in one model and in the other by administration of paracetamol (300 mg kg(-1) in saline) orally, after a 16-h fast. An aqueous extract of the whole plant (0.9 g kg(-1)) was used on a pre- and post-treatment basis. Asteracantha reduced the alanine aminotransferase (ALT) level by 69.32% (P < 0.001) and increased the liver reduced glutathione level by 64.65% (P < 0.001) in the pre-treated group, 4 days after the administration of CCl4. A similar pattern was observed in the pre-treated group 4 h after the administration of paracetamol with a reduction in serum levels of ALT, aspartate aminotransferase and alkaline phosphatase enzymes by 65.04, 55.79 and 45.75% respectively (P < 0.001). Plant extract also increased the glutathione concentration of the liver significantly (P < 0.001). Histopathological studies also provided supportive evidence for results from the biochemical analysis with marked improvement in liver architecture being observed in the Asteracantha-treated groups. Pre-treatment showed better results than post-treatment in both hepatotoxic models. Overall results indicate that the aqueous extract of Asteracantha longifolia possesses hepatoprotective effects on CCl4- and paracetamol-induced hepatotoxicity in mice.

Protection by Osbeckia aspera against carbon tetrachloride-mediated alterations in microsomal drug metabolizing enzyme activity.

Previous investigations have confirmed the protective effect of Osbeckia aspera leaf extract on carbon tetrachloride-mediated liver injury in rat models. It is well known that the earliest alterations in liver cell structure and function following carbon tetrachloride poisoning involve the endoplasmic reticulum and its drug metabolizing enzymes. Therefore, we investigated whether an aqueous leaf extract of O. aspera could offer protection against carbon tetrachloride-induced changes in the microsomal drug metabolizing enzymes aniline hydroxylase and p-aminopyrine N-demethylase. This enzyme activity was compared with phenobarbital-induced righting reflex and lipid peroxidation. Treatment of rats with the aqueous leaf extract of O. aspera (before or after the administration of carbon tetrachloride) resulted in a marked decrease in carbon tetrachloride-mediated alterations in aniline hydroxylase and p-aminopyrine N-demethylase activity, phenobarbital-induced loss of righting reflex and malondialdehyde formation due to lipid peroxidation. The Km value of these enzymes in control and Osbeckia-treated rats were the same. These results show that the plant extract can markedly decrease the carbon tetrachloride-mediated reduction in aniline hydroxylase and p-aminopyrine N-demethylase activity and inhibit peroxidative damage to the cell membrane. Phenobarbital-induced sleeping time in rats and kinetic enzyme studies suggested that the effects of the plant extract was neither due to an induction of the drug-metabolizing enzymes under investigation, nor due to an alteration in the Km values of these enzymes.

Effect of Melothria maderaspatana on carbon tetrachloride-induced changes in rat hepatic microsomal drug-metabolizing enzyme activity.

Treatment with an aqueous extract of the aerial parts of Melothria maderaspatana, before or after CCl4 administration in rats markedly decreased CCl4-mediated reductions in aniline hydroxylase and p-aminopyrine N-demethylase activities. Phenobarbital-induced sleeping time in rats and kinetic enzyme studies showed that the effect of the plant was neither due to an induction of the drug metabolizing enzymes nor due to an alteration in the Km values of the enzymes.

Evaluation of the efficacy of Melothria maderaspatana in the alleviation of carbon tetrachloride-induced liver dysfunction.

An investigation was carried out to evaluate the ability of Melothria maderaspatana to protect the livers of albino rats from carbon tetrachloride-mediated alterations in liver histopathology and serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. Treatment with an aqueous extract of Melothria aerial parts (either before or after CCl4 administration) markedly decreased CCl4-mediated alterations in liver histopathology as well as serum enzyme levels. Results provide supportive evidence for the folklore view that this plant is a good hepatotonic.