Reduction-Triggered Doxorubicin Delivery by Self-Assembled Nanospheres of Lipoylated Caffeine.

This study reports a new amphiphilic bioconjugate (CAFF-LA) derived from the lipoylation of a hydroxyethyl derivative of caffeine. In water, CAFF-LA self-assembles into nanospheres with an average size of 155 nm, as evidenced from dynamic light scattering and electron microscopy studies. The nanospheres are stable in serum and could be disintegrated upon exposure to the reducing environment of dithiothreitol (DTT; 10 mM) and glutathione (GSH; 10 mM). These nanospheres easily encapsulate the chemotherapy medication, doxorubicin (DOX), and demonstrate an efficacious transport into doxorubicin-resistant cervical cancer (HeLa) cells, wherein a marked induction in apoptosis and significantly lower IC50 have been observed when compared to that of free drug. The in vitro assessment of cell viability and hemocompatibility present these nanospheres as potentially safe and efficient intracellular reduction stimulus-responsive drug-delivery vehicles.

Effect of ß-cyfluthrin (synthetic pyrethroid) on learning, muscular coordination and oxidative stress in Swiss albino mice.

The present study was planned to evaluate neurotoxic effects of ß-cyfluthrin in female Swiss albino mice. Two doses of ß-cyfluthrin, specifically, one-tenth of median lethal dose (LD50) and one-twentieth of LD50, were selected for the study. Open-field behaviour, exploratory behaviour and emotional status were affected, and animals showed anxiety-like behaviour after ß-cyfluthrin administration. Spatial learning was decreased using the Hebb-Wiliams maze. Acetylcholinesterase enzyme activity significantly decreased in the treated animals. The administration of ß-cyfluthrin caused increased lipid peroxidation (malondialdehyde) and decreased superoxide dismutase, catalase and glutathione peroxidase activity in brain tissue. In conclusion, ß-cyfluthrin caused neurotoxicity as well as oxidative damage in the brain of Swiss albino mice at the tested dose levels.

Bifenthrin-induced neurotoxicity in rats: involvement of oxidative stress.

Extensive use of synthetic pyrethroids has resulted in serious human health issues. Induction of oxidative stress is an important mechanism of action of most pesticides including pyrethroids. In the present study, we have elucidated the possible role of oxidative stress in bifenthrin-induced neurotoxicity. Adult male Wistar rats were administered bifenthrin (3.5 and 7 mg per kg body weight p.o.) for 30 days. Behavioral studies were conducted on a set of randomly selected rats from each treatment group after completion of treatment. Neurochemical parameters were assessed 24 h after the last dose was administered. The selected behavioral and neurochemical endpoints were also assessed 15 days after cessation of exposure to reveal whether the neurobehavioral changes produced by bifenthrin were temporary or permanent. Deficits in motor activity, motor incoordination, and cognitive impairment were observed after exposure to bifenthrin. Levels of biogenic amines viz. dopamine (DA) and its metabolites, i.e. 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), epinephrine (EPN), norepinephrine (NE), and serotonin (5-HT) altered in the frontal cortex, corpus striatum, and hippocampus of bifenthrin-treated rats. A decrease in the activity of acetylcholinesterase (AChE) occurred in all regions of the brain. Both doses of bifenthrin significantly induced lipid peroxidation (LPO) and increased protein carbonyl levels in the frontal cortex, corpus striatum, and hippocampus of rats. The activities of antioxidant enzymes, i.e. catalase, superoxide dismutase, and glutathione peroxidase, were also suppressed in all selected regions of the brain. A trend of recovery was, however, observed in all the behavioral and neurochemical endpoints 15 days after withdrawal of exposure. Oxidative stress seems to play an important role in bifenthrin-induced neurotoxicity. Our study suggests that long-term exposure to these compounds can produce detrimental effects.

Curcumin modulates oxidative stress and genotoxicity induced by a type II fluorinated pyrethroid, beta-cyfluthrin.

Present study examines the possibility of ß-cyfluthrin (ß-CYF) induced oxidative stress, genotoxicity, histopathological alterations and the role of curcumin (CUR) in alleviating its toxic effects. CUR is a naturally occurring phenolic compound of turmeric (Curcuma longa) and is used as a spice, food-coloring agent and in cosmetics and medicines. CUR provides vital protection against many pathological conditions due to its antioxidant and anti-inflammatory properties. Male Swiss albino mice were distributed into six groups, I: control, II: CUR (0.2%), III: ß-CYF low dose (1/20 of LD50), IV: ß-CYF high dose (1/10 of LD50), V: ß-CYF low dose + CUR and VI: ß-CYF high dose + CUR. Mice were orally administered their respective doses daily for 21 days. ß-CYF caused elevation in AST, ALT, LPO and decline in GPx, CAT and SOD activities. A significant decrease in MI and increase in chromosomal aberrations, TL, TI and TM was recorded in ß-CYF exposed groups. CUR co-administration modulated AST, ALT, LPO, GPx, CAT and SOD activity. CUR supplementation improved the MI and reduced the chromosomal aberrations, TL, TI and TM. ß-CYF caused serious pathological alterations in liver and these were alleviated by CUR. It is concluded that CUR scavenges ROS and renders a protection against ß-CYF genotoxicity.