AIM OF THE STUDY: The study is aimed at identifying the key ingredients of papaya leaf extract and elucidate the mechanism (s) of action of the identified potent component in mitigating thrombocytopenia (Thp).
MATERIALS AND METHODS: C. papaya leaf juice was subjected for sequential fractionation to identify the anti-thrombocytopenic phytochemicals. In vivo, stable thrombocytopenia was induced by subcutaneous injection of 70 mg/kg cyclophosphamide (Cyp). After induction, rats were treated with 200 and 400 mg/kg body weight papaya leaf juice and with identified fractions for 14 days. Serum thrombopoietin level was estimated using ELISA. CD110/cMpl, a receptor for thrombopoietin on platelets was measured by western blotting.
RESULTS: Administration of cyclophosphamide for 6 days induced thrombocytopenia (210.4 ± 14.2 × 103 cells/μL) in rats. Treating thrombocytopenic rats with papaya leaf juice and butanol fraction for 14 days significantly increased the platelet count to 1073.50 ± 29.6 and 1189.80 ± 36.5 × 103 cells/μL, respectively. C.papaya extracts normalized the elevated bleeding and clotting time and decreased oxidative markers by increasing endogenous antioxidants. A marginal increase in the serum thrombopoietin (TPO) level was observed in Cyp treated group compared to normal and treatment groups. Low expression of CD110/cMpl receptor found in Cyp treated group was enhanced by C. papaya extracts (CPJ) and CPJ-BT. Furthermore, examination of the morphology of bone marrow megakaryocytes, histopathology of liver and kidneys revealed the ability of CPJ and fractions in mitigating Cyp-induced thrombocytopenia in rats.
CONCLUSION: C. papaya leaf juice enhances the platelet count in chemotherapy-induced thrombocytopenia by increasing the expression of CD110 receptor on the megakaryocytes. Hence, activating CD110 receptor might be a viable strategy to increase the platelet production in individuals suffering from thrombocytopenia.
MATERIALS AND METHODS: Participants with an estimated glomerular filtration rate of 30 to <90 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio of >300-5,000 mg/g were randomized to 100 mg of canagliflozin or a placebo. The effects of canagliflozin treatment on pre-specified efficacy and safety outcomes were examined using Cox proportional hazards regression between participants from EA countries (China, Japan, Malaysia, the Philippines, South Korea and Taiwan) and the remaining participants.
RESULTS: Of 4,401 participants, 604 (13.7%) were from EA countries; 301 and 303 were assigned to the canagliflozin and placebo groups, respectively. Canagliflozin lowered the risk of primary outcome (composite of end-stage kidney disease, doubling of serum creatinine level, or renal or cardiovascular death) in EA participants (hazard ratio 0.54, 95% confidence interval 0.35-0.84). The effects of canagliflozin on renal and cardiovascular outcomes in EA participants were generally similar to those of the remaining participants. Safety outcomes were similar between the EA and non-EA participants.
CONCLUSIONS: In the CREDENCE trial, the risk of renal and cardiovascular events was safely reduced in participants from EA countries at high risk of renal events.
METHODS: Pressurized hot water extraction P. tenellus was carried out and standardized to 7.9% hydrosable tannins. In vitro toxicity of the extract was tested on NIH 3 T3 cell by MTT assay. The cellular antioxidant level was quantified by measuring cellular level of glutathione. Oral sub-chronic toxicity (200, 1000 and 3000 mg/kg body weight) of P. tenellus extract were evaluated on healthy mice. Liver and kidney antioxidant level was quantified by measuring levels of Ferric Reducing Antioxidant Potential (FRAP), superoxide dismutase, glutathione.
RESULTS: The P. tenellus extract did not induce cytotoxicity on murine NIH 3 T3 cells up to 200 μg/mL for 48 h. Besides, level of glutathione was higher in the extract treated NIH 3 T3 cells. P. tenellus extract did not cause mortality at all tested concentration. When treated with 1000 mg/kg of the extract, serum liver enzymes (ALP and ALT) and LDH were lower than normal control and mice treated with 200 mg/kg of extract. Moreover, SOD, FRAP and glutathione levels of liver of the mice treated with 200 and 1000 mg/kg of extract were higher than the normal control mice. On the other hand, when treated with 3000 mg/kg of extract, serum liver enzymes (ALP and ALT) and LDH were higher than normal mice without changing the liver SOD and glutathione level, which may contribute to the histological sign of ballooning hepatocyte.
CONCLUSION: P. tenellus extract standardized with 7.9% hydrosable tannins and their catabolites increased the antioxidant levels while reducing the nitric oxide levels in both liver and kidney without causing any acute and sub-chronic toxicity in the mice.
OBJECTIVE: To investigate the effect of administration of VCO on lipid profile, markers of hepatic and renal dysfunction, and hepatic and renal antioxidant activities of alloxan induced diabetic rats.
METHODS: Twenty-four male albino rats were used, and they were divided into four groups of six rats each. Group 1 (Normal Control, NC) received distilled water (1 mL/kg); Group 2 (VCO Control) received VCO (5 mL/kg); Group 3 (Diabetic Control, DC) received distilled water (1 mL/kg); Group 4 (Test Group, TG) received 5 ml/kg of VCO.
RESULTS: There were no significant differences in blood glucose, body weights, relative liver weights, relative kidney weights, hepatic and renal Superoxide Dismutase (SOD) activities, Malondialdehyde (MDA), albumin, aspartate Amino Transaminase (AST), alanine Amino Transaminase (ALT), Alkaline Phosphatase (ALP), urea, creatinine, uric acid, total cholesterol, triacylglycerol, Very Low Density Lipoprotein cholesterol (VLDL) and Low Density Lipoprotein cholesterol (LDL) concentrations; significant increases in renal Glutathione (GSH), hepatic catalase, Glutathione Peroxidase (GPx) and GSH but significant reduction in renal GPx and catalase activities of VCO control group compared with NC group. There were significant increases in blood glucose, relative liver and kidney weights, hepatic GPx, hepatic and renal MDA concentration, ALP, AST, ALT, urea, creatinine, uric acid, triacylglycerol, total cholesterol, LDL and VLDL concentrations; and significant decreases in body weight, hepatic SOD and GSH activities and albumin concentration but no significant difference in hepatic catalase activity of DC group compared with NC group. Administration of VCO to diabetic rats positively modulated these parameters compared with the diabetic control.
CONCLUSION: The study showed the potentials of VCO in the management of hyperlipidemia, renal and hepatic dysfunctions imposed by hyperglycemia and by oxidative stress in diabetic rats.