Periplogenin‐3‐O‐ ‐D‐Glucopyranosyl ‐(1→6)‐ ‐D‐Glucopyaranosyl‐ ‐(1→4) ‐D‐Cymaropyranoside,Isolated from Aegle marmelos Protects Doxorubicin Induced Cardiovascular Problems and Hepatotoxicity in Rats

Doxorubicin is a common chemotherapeutic anticancer drug. Its use is associated with adverse effects including cardiotoxicity. Several therapeutics interventions have been attempted to reduce the toxicity and to improve the efficacy of the drug. However, on phytochemicals very few investigations have been made. In the present study we have evaluated the potential of a cardenolide, periplogenin, isolated from the leaves of Aegle marmelos in protecting the doxorubicin induced cardiotoxicity and lipid peroxidation (LPO) in rats. Doxorubicin induced cardiac and hepatotoxicity were characterized by marked biochemical changes including an increase in serum creatine kinase–MB (CK–MB), glutamate‐pyruvate transaminase (SGPT), and tissue LPO, with a decrease in superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). It also increased the levels of different serum lipids, but decreased the amount of high‐density lipoprotein (HDL). Cotherapy of the test cardenolide and doxorubicin for 4 weeks reversed all these adverse effects. However, out of three different concentrations (12.5, 25, and 50 mg/kg p.o.) of the test periplogenin, 25 mg/kg appeared to be most effective. When its efficacy was compared with that of vitamin E (α‐tocopherol) the isolated compound exhibited a better therapeutic potential. The isolated periplogenin from the leaves of A. marmelos could potentially inhibit doxorubicin‐induced cardiovascular problems in rats. However, its moderate dose was found to be most effective.     

Analysis of N1‐acetyl‐N2‐formyl‐5‐methoxykynuramine/N1‐acetyl‐5‐methoxy‐kynuramine formation from melatonin in mice

Abstract: The interactions of melatonin, a potent endogenous antioxidant, with reactive oxygen species generate several products that include N¹‐acetyl‐N²‐formyl‐5‐methoxykynuramine (AFMK) and N¹‐acetyl‐5‐methoxy‐kynuramine (AMK). The physiological or pathological significance of AFMK/AMK formation during the process of melatonin metabolism in mammals has not been clarified. Using a metabolomic approach in the current study, the AFMK/AMK pathway was thoroughly investigated both in mice and humans. Unexpectedly, AFMK and AMK were not identified in the urine of humans nor in the urine, feces or tissues (including liver, brain, and eyes) in mice under the current experimental conditions. Metabolomic analysis did identify novel metabolites of AMK, i.e. hydroxy‐AMK and glucuronide‐conjugated hydroxy‐AMK. These two newly identified metabolites were, however, not found in the urine of humans. In addition, oxidative stress induced by acetaminophen in the mouse model did not boost AFMK/AMK formation. These data suggest that AFMK/AMK formation is not a significant pathway of melatonin disposition in mice, even under conditions of oxidative stress.     

Thyroid dysfunction in patients with chronic hepatitis C: Virus‐ or therapy‐related?

Background and Aims:  Thyroid dysfunction (TD) represents an extrahepatic manifestation of chronic hepatitis C (CHC). Moreover, the currently approved treatment of CHC is often associated with TD. However, it remains debatable if TD is mainly virus- or treatment-related. The aim of this study was to assess the incidence and features of TD, and to identify its predictors in treated and untreated CHC patients.
Methods:  Ninety-four patients with CHC and normal thyroid function were evaluated long-term for TD: 33 were untreated (control group) and 61 were treated with pegylated interferon alpha (PEG-IFN-α) plus ribavirin (treatment group). Mean follow up was 80.1 and 39.4 months, respectively.
Results:  All patients in the control group remained euthyroid, while 13 treated patients (21.3%) developed TD ( P  < 0.001). Eleven of these were diagnosed with hypothyroidism and two with hyperthyroidism, which then converted to hypothyroidism. In the majority of cases (9/13, 69.2%) TD did not reverse after treatment discontinuation and required hormone replacement therapy. Pretreatment virological parameters did not predict TD, according to multiple logistic regression analysis. TD was not associated with total dose of PEG-IFN-α or ribavirin, viral kinetics or with virological outcome, but it was linked to development of other therapy-related autoimmune disorders (odds ratio, 8.29).
Conclusion:  Antiviral therapy of CHC possibly induces de novo or exacerbates pre-existing silent TD. TD does not seem to correlate with any pretreatment virological parameter; it is probably not related to dose or treatment duration, nor linked to viral kinetics or virological outcome. The role of chronic hepatitis C per se in TD remains to be determined.