W. C. Kershaw

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Susceptibility to cadmium (Cd) hepatotoxicity differs among inbred strains of mice. For example, C3H/HeJ mice are sensitive to Cd-induced hepatotoxicity, whereas DBA/2J mice are resistant. The mechanism of genetic predisposition to Cd hepatotoxicity is unknown. A contemporary theory for acute target organ intoxication maintains that Cd initially damages(More)
The effect of Zn-induced metallothionein (MT) on the toxicity, uptake, and subcellular distribution of cadmium (Cd) was examined in rat primary hepatocyte cultures and compared to results obtained earlier in this laboratory from intact animals. Hepatocytes were isolated and grown in monolayer culture for 22 h and subsequently treated with ZnCl2 (100 μM) for(More)
The purpose of this study was to determine if Zn pretreatment could protect rat primary hepatocyte cultures from the cytotoxicity of five metals that have little or no affinity for metallothionein (MT). Hepatocytes were grown in monolayer cultures for 22 h and subsequently treated with ZnCl2 (100 microM) for 24 h; which increased the MT concentration(More)
The purpose of this study was to quantitate hepatic metallothionein-I (MT-I) and metallothionein-II (MT-II) in adult mice pretreated with various dosages of selected inorganic and organic compounds and in nonchemically treated neonatal mice. Male CF-1 mice received Zn (0.38-6.0 mmol/kg, sc), Cd (5-80 mumol/kg, sc), dexamethasone (10-1000 mumol/kg, sc), or(More)
The present investigation examines the possibility that Cd and ethanol have a significant toxicological interaction. This examination was warranted as exposure to either chemical is known to compromise human health. Inasmuch as both chemicals affect the morphology, biochemistry, and physiology of liver, it seemed reasonable to consider liver as a possible(More)
Metallothionein (MT), a low-molecular-weight, cysteine-rich, metal-binding protein, has been implicated in the detoxification of Cd. However, whether MT protects against the cellular toxicity of other metals has not been examined thoroughly. This study was therefore designed to determine the effects of Zn-induced MT on the toxicity of seven metals in rat(More)
Degradation of metallothionein (MT) from rat liver was examined. Degradation of apo-MT by liver homogenate was greater than that by cytosol. At pH 5.5, degradation by homogenate was more than that at pH 7.2. These findings suggest that proteases that function at acidic pH are probably involved in MT degradation. Because lysosomes are the principal(More)
Recently, our laboratory demonstrated that metallothionein-1 (MT-1) is degraded faster than metallothionein-2 (MT-2) in liver of Zn-treated adult rats; however, it is not clear whether this phenomenon is unique to Zn treatment or the age of the animal. Furthermore, many investigators maintain that the degradation of MT is regulated by its metal composition.(More)
Susceptibility to Cd toxicity differs among inbred strains of mice. For example, C3H/He mice are sensitive to Cd-induced hepatotoxicity while DBA/2 mice are resistant. Metallothionein (MT), which in rodents exists predominantly as two isoproteins (MT-I and MT-II), is an important endogenous protein in the detoxication of Cd. The present investigation(More)
Flavone (1) was found to protect against ethanol-induced gastric damage in rats; however, it is known that certain compounds in the flavone class, including flavone itself, are inducers of hepatic drug metabolizing enzymes. With the hope of identifying gastroprotective flavones that have minimal effects on drug metabolizing enzymes, we have synthesized and(More)