Evaluation of anti-cancer effect of zerumbone and cisplatin on N-nitrosodiethylamine induced hepatic cancer in freshwater fish (Danio rerio).

Cancer is the uncontrolled proliferation of abnormal cells in the body. There is a foreseeable need for an effective anti-carcinogenic drug. In this regard, zerumbone (ZER) is identified as one such therapeutic herbal compound that has been shown to enhance the anticancer activity of cisplatin (CIS), with negligible side effects. Yet, the fundamental mechanisms of co-treatment of ZER and CIS on Hepatocellular carcinoma remain indefinable. The current study is endeavored to evaluate the anti-cancer effect of the individual and co-treatment of ZER, CIS and its combination on Diethyl nitrosamine induced hepatic cancer in wild-type zebra fish (Danio Rerio) models. Our careful analysis on treated and untreated fishes shows that CIS + ZER combination group restricted further progression of hepatocellular carcinoma cells significantly, which concludes that co-treatment of ZER with CIS was therapeutically effective for treating human HCC cancer cells which were induced into zebra fish.

Age associated changes in erythrocyte membrane surface charge: Modulatory role of grape seed proanthocyanidins.

Aging, a multifactorial process of enormous complexity is characterized by impairment of physio-chemical and biological aspects of cellular functions. It is closely associated with increased free radical production, which situation ultimately leads to devastation of normal cell function and membrane integrity. The present study was aimed to determine the effect of proanthocyanidins rich grape seed extract (GSP) on membrane surface charge density in erythrocytes during animal age associated oxidative stress. GSP (100 mg/day/kg body weight) was administered orally for 15 and 30 days to young and aged rats. Significant decrease in surface charge levels with concomitant increase in protein carbonyls and decrease in glycoprotein, antioxidants status was noted in erythrocytes of aged rats when compared with young rat erythrocytes. Duration dependent supplementation of GSP increased the erythrocyte surface charge density to near normalcy in aged rats. Decrease in protein carbonyls level and increase in glycoproteins as well as antioxidant status was observed in aged rat erythrocytes on GSP treatment. Thus, from our results, we conclude that GSP is an effective anti-aging drug in preventing the oxidative stress associated loss of membrane surface charge, which thereby maintains the erythrocyte membrane integrity and functions in elderly.

Rejuvenation of antioxidant system in central nervous system of aged rats by grape seed extract.

Oxidative stress is considered as a major risk factor that contributes to age-related increase in lipid peroxidation and declined antioxidants in the central nervous system during aging. Grape seed extract, one of the bioflavonoid, is widely used for its medicinal properties. In the present study, we evaluated the role of grape seed extract on lipid peroxidation and antioxidant status in discrete regions of the central nervous system of young and aged rats. Male albino rats of Wistar strain were divided into four groups: Group I-control young rats, Group II-young rats treated with grape seed extract (100 mg/kg body weight) for 30 days, Group III-aged control rats and Group IV-aged rats supplemented with grape seed extract (100 mg/kg body weight) for 30 days. Age-associated increase in lipid peroxidation was observed in the spinal cord, cerebral cortex, striatum and the hippocampus regions of aged rats (Group III). Activities of antioxidant enzymes like superoxide dismutase, catalase, glutathione peroxidase and levels of non-enzymic antioxidants like reduced glutathione, Vitamin C and Vitamin E were found to be significantly decreased in all the brain regions studied in aged rats when compared to young rats. However, normalized lipid peroxidation and antioxidant defenses were reported in the grape seed extract-supplemented aged rats. These findings demonstrated that grape seed extract enhanced the antioxidant status and decreased the incidence of free radical-induced lipid peroxidation in the central nervous system of aged rats.

Modulation of age-associated oxidative DNA damage in rat brain cerebral cortex, striatum and hippocampus by L-carnitine.

The free radical theory of cell aging may have significant relevance in the pathogenesis of a number of age-related neurological disorders. A large body of experimental evidence supports the existence of a relationship between genomic instability, DNA damage and aging. The age-associated accumulation of oxidative DNA damage is well documented in central nervous system. The decline of mitochondrial respiratory function and loss of normal cellular homeostasis as consequences of excessive accumulation of endogenous oxidative damages to DNA have long been indicated in the aging process. In the present study, age-associated alterations in the content of DNA and accumulation of oxidative DNA damage products such as 8-OHdG and DNA protein cross-links are mainly focused. In parallel, we have also investigated the salubrious effect of l-carnitine against oxidative DNA damage as it possesses energy and antioxidant improving properties. Our results thus reveal that L-carnitine has inhibiting effect on the accumulation of age-related oxidative DNA damage in various brain regions, viz. cerebral cortex, striatum and hippocampus.

Age-dependent alterations in mitochondrial enzymes in cortex, striatum and hippocampus of rat brain -- potential role of L-Carnitine.

Mitochondria link the energy -- releasing activities of electron transport and proton pumping with the energy conserving process of oxidative phosphorylation to form ATP. A declined mitochondrial performance has been generally observed during aging. In the present investigation, the activities of tricarboxylic acid cycle enzymes such as isocitrate, alpha-ketoglutarate, succinate and malate dehydrogenases and electron transport complexes I-IV were measured in mitochondria isolated from brain regions like cortex, striatum and hippocampus of young and aged rats before and after L-Carnitine supplementation. All the three brain regions of aged rats showed decreased activities of isocitrate, alpha-ketoglutarate and succinate dehydrogenases, complexes I and IV when compared to control young rats. Striatum seems to be the most susceptible region when compared to hippocampus and cortex. L-Carnitine supplementation to aged rats reversed the activities of these enzymes to near normal whereas treatment to young rats did not show any significant alterations. These results confirm that L-Carnitine can alleviate the age-associated decline in the metabolic efficiency of mitochondria in all three brain regions under investigation.