Influence of gender on cocaine hepatotoxicity in CF-1 mice.

Gender is known to play a role in the bioavailability, metabolism, and lethality of many toxic substances. This study was conducted to investigate the influence of gender on cocaine hepatotoxicity (CH) and lipopolysaccharide (LPS) potentiation of CH. Male and female CF-1 mice were orally administered 20 mg/kg body weight cocaine hydrochloride once daily for 7 days.

Plasma butyrylcholinesterase activity protects against cocaine hepatotoxicity in female mice.

Oral cocaine administration results in hepatic necrosis, increased plasma transaminase concentration, and decreased antioxidative capability, which is potentiated by lipopolysaccharide (LPS) in male CF-1 mice. Females administered the same treatment regimen display none of the hepatotoxic effects seen in their male counterparts. This study was conducted to further dissect the mechanism responsible for this gender difference in cocaine hepatotoxicity (CH) and lipopolysaccharide potentiation of CH.

Gender differences in cocaine pharmacokinetics in CF-1 mice.

Hepatocellular damage is thought to occur as a result of cytochrome P450-mediated oxidation of cocaine to norcocaine (NC), a precursor of the hepatotoxic nitrosonium ion. However, this damage occurs only in male mice, with females exhibiting minimal biochemical and histological signs of hepatocellular stress. The objective of this study was to determine the plasma time course and tissue disposition of cocaine and its metabolites to further investigate the role that metabolism may play in the gender difference observed.

Cocaine hepatotoxicity and its potentiation by lipopolysaccharide: treatment and gender effects.

This study was conducted to investigate the effect of a 7-day treatment as well as the influence of gender on cocaine hepatotoxicity (CH). Lipopolysaccharide (LPS) potentiation of CH was also investigated. Male and female CF-1 mice were orally administered 20 mg/kg body weight cocaine hydrochloride once daily for 7 days.

Endotoxin potentiates cocaine-mediated hepatotoxicity by nitric oxide and reactive oxygen species.

Exposure to small, noninjurious doses of the inflammagen, bacterial endotoxin (lipopolysaccharide, LPS) augments the toxicity of certain hepatotoxicants, including cocaine. The mechanism of this interaction has not been clearly elucidated, but it seems that aspects of the inflammatory response initiated by exposure to LPS may be responsible. In particular, this study examined the role of Kupffer cells and the modulating effects of nitric oxide (NO) and reactive oxygen species (ROS) on the LPS potentiation of cocaine-mediated hepatotoxicity (CMH).

Immunomodulation by cocaine and ketamine in postnatal rats.

The abuse of cocaine (COC) in combination with ketamine (KET) among pregnant women was shown to be high. Transplacental exposure is not the only route by which a newborn may be exposed to these agents, but they can also distribute into breast milk. Chronic COC exposure is associated with immunological modulation in human and animal models.

Effect of a chemical mixture on dermal penetration of arsenic and nickel in male pig in vitro.

The effect of a chemical mixture on the dermal penetration of arsenic or nickel was assessed by applying arsenic-73 or nickel-63 alone or with the chemical mixture to dermatomed male pig skin samples in flow-through diffusion cells. The chemical mixture consisted of chloroform, phenanthrene, and toluene for arsenic penetration studies and phenol, toluene, and trichloroethylene (TCE) for nickel studies. These are predominant chemicals found at hazardous waste sites.

N-acetylcysteine pretreatment decreases cocaine and endotoxin-induced hepatotoxicity.

Cocaine produces hepatotoxicity by a mechanism that remains undefined but has been linked to its oxidative metabolism. Endotoxin (lipopolysaccharide, LPS) is also a well-known cause of hepatic damage, and exposure to noninjurious doses of LPS increases the toxicity of certain hepatotoxins. Previously it was demonstrated that exposure to noninjurious doses of LPS dramatically increases cocaine-mediated hepatotoxicity (CMH).

Inhibition of cocaine oxidative metabolism attenuates endotoxin potentiation of cocaine mediated hepatotoxicity.

The oxidative metabolism of cocaine by the microsomal monooxygenase enzymes has been postulated to be essential for cocaine mediated hepatotoxicity (CMH). Endotoxin (lipopolysaccharide, LPS), a well-known cause of hepatic damage, previously has been demonstrated to dramatically increase CMH. The mechanism of this interaction has not been clearly elucidated, but cocaine oxidative metabolism appears to sensitize hepatocytes so that subsequent exposure to small amounts of LPS can further augment CMH.

Endotoxin potentiates the hepatotoxicity of cocaine in male mice.

Cocaine produces hepatotoxicity by a mechanism that remains undefined but that has been linked to its oxidative metabolism. Endotoxin (lipopolysaccharide, LPS) is also a well-known cause of hepatic damage, where exposure to non-injurious doses of LPS increases the toxicity of certain hepatotoxins. This study was conducted to investigate the possible potentiation of cocaine-mediated hepatotoxicity (CMH) by LPS.