Renal toxicity

In rats given HgCl2, an increase in renal Ca concentration was observed (Gritzka and Trump 1968 Weinberg et al. 1989) and the increase in renal 

A stimulatory effect of Hg on release of mitochondrial Ca has also been observed in rat kidney mitochondria (Chavez and Holguim 1988). Chavez and his collaborators concluded that the Hg -induced Ca release may be due to the modification of sulfhydryl groups of mitochondrial membrane proteins (Chavez and Holguin 1988 Chavez et al. 1989, 1991). 

The lethal toxicity of Hg was significantly prevented by preinduction of MT synthesis (Yamane et al. 1977). Renal MT may bind to Hg and suppress its toxic action in the kidney cells. GSH may also be a major determinant of Hg toxicity. Depletion of GSH by treatment of mice with an inhibitor of GSH synthesis markedly enhanced (about tenfold) the lethal and renal toxicity of HgCl2 (Naganuma et al. 1990). 

Selenium (Se), an essential trace element, has a protective effect against Hg toxicity. Coadministration of a selenium compound with Hg resulted in remarkable depression of acute toxicity of Hg through the formation of stable complexes of Hg and Se in various tissues such as liver and kidney (Naganuma and Imura 1980a, 1981, 1984a). 

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Health and Safety Factors. Boron trifluoride is primarily a pulmonary irritant. The toxicity of the gas to humans has not been reported (58), but laboratory tests on animals gave results ranging from an increased pneumonitis to death. The TLV is 1 ppm (59,60). Inhalation toxicity studies in rats have shown that exposure to BF at 17 mg/m resulted in renal toxicity, whereas exposure at 6 mg/m did not result in a toxic response (61). Prolonged inhalation produced dental fluorosis (62). High concentrations bum the skin similarly to acids such as HBF and, if the skin is subject to prolonged exposure, the treatment should be the same as for fluoride exposure and hypocalcemia. No chronic effects have been observed in workers exposed to small quantities of the gas at frequent intervals over a period of years. 

Adverse side effects of gold treatments include stomatitis, rash, and proteinuria. Complete blood counts and urinalysis should be performed before each or every other injection of gold compounds. Pmritic skin rash and stomatitis are more common adverse effects that may resolve, if therapy is withheld for a few weeks and then restarted cautiously at a lower dose. Oral gold causes less mucocutaneous, bone marrow, and renal toxicity than injectable gold, but more diarrhea and other gastrointestinal reactions appear. 

Isoflurane is a respiratory depressant (71). At concentrations which are associated with surgical levels of anesthesia, there is Htde or no depression of myocardial function. In experimental animals, isoflurane is the safest of the oral clinical agents (72). Cardiac output is maintained despite a decrease in stroke volume. This is usually because of an increase in heart rate. The decrease in blood pressure can be used to produce "deHberate hypotension" necessary for some intracranial procedures (73). This agent produces less sensitization of the human heart to epinephrine relative to the other inhaled anesthetics. Isoflurane potentiates the action of neuromuscular blockers and when used alone can produce sufficient muscle relaxation (74). Of all the inhaled agents currently in use, isoflurane is metabolized to the least extent (75). Unlike halothane, isoflurane does not appear to produce Hver injury and unlike methoxyflurane, isoflurane is not associated with renal toxicity. 

Cumulative organ toxicity also presents a significant obstacle for effective chemotherapy. In many cases, the severity of the toxicity impedes the broader use of an agent. Other specific toxicities are associated with specific agents, for example cardiotoxicity with adriamycin (32), renal toxicity with i7j -platinum (28), and neurotoxicity with vincristine (49). 

The drug SC-558 acts by a fourth mechanism, specifically inhibiting COX-2. It is a weak competitive inhibitor of COX-1 but inhibits COX-2 in a slow, time-dependent process. Specific COX-2 inhibitors will likely be the drugs of the future because they selectively block the inflammation mediated by COX-2, without the potential for stomach lesions and renal toxicity that arise from COX-1 inhibition. 

There have been no reports of renal toxicity associated with acute inhalation exposure to endosulfan in laboratory animals. However, acute oral and dermal exposure to endosulfan has been reported to cause damage to the kidneys of rats, rabbits, and dogs (FMC 1958, 1980a Gupta and Chandra 1975 Hoechst... 

Encapsulation of cDDP in liposomes did not show such favorable effects. Liposome encapsulation of cDDP decreased the antitumor effect (Fig. 9). It was demonstrated that administration of cDDP liposomes resulted in a lower incidence as well as reduced severity of focal alterations of the epithelium of the proximal tubuli compared to administration of the free drug (Steerenberg et al., 1988). However, despite this reduction in renal toxicity the therapeutic index... 

Route Dependent Toxicity. The toxicity of trichloroethylene does not seem to be heavily dependent upon its route of entry. Inhalation and ingestion are the primary exposure routes, and the liver, heart, and central nervous system are the primary targets for both routes (Candura and Faustman 1991). Renal toxicity results principally from oral exposure, and dermal exposure generally confines its toxic effects to the skin, although broad systemic effects can be induced imder conditions of high exposure (Bauer and Rabens 1974). Attributing such effects solely to dermal exposure, however, is difficult because inhalation exposure is often a factor in these cases as well. 

Duration should be <2 wk to avoid systemic accumulation and renal toxicity... 

NSAIDs are classified as non-selective (they inhibit COX-1 and COX-2) or selective (they inhibit only COX-2) based on degree of cyclooxygenase inhibition. COX-2 inhibition is responsible for anti-inflammatory effects, while COX-1 inhibition contributes to increased GI and renal toxicity associated with non-selective agents. Since the antiplatelet effect of non-selective NSAIDs is reversible, concurrent use may reduce the... 

Vancomycin Infusion related toxicity (phlebitis, red man syndrome) Potential for additive renal toxicity if being coadministered with a nephrotoxic agent (e.g., aminoglycoside) monitor renal function (BUN/SCr) weekly in stable patients Consider vancomycin troughs to ensure therapeutic concentrations ... 

Methotrexate Myelosuppression, stomatitis Diarrhea, nausea, vomiting, renal toxicity... 

Cisplatin-docetaxel diarrhea, cardiac toxicity, renal toxicity, neuropathy, weakness, hypersensitivity reactions, anemia Infection, thromocytopenia, nausea, vomiting, diarrhea, cardiac, High (day 1 only)... 

Information is available on the renal toxicity of ingested lead in several species, including rats, dogs, monkeys, and rabbits. The results indicate that histopathological changes in the kidneys of lead-treated animals are similar to those in humans (see Section 2.2.1.2). Reduced glomerular filtration rates and aminoaciduria were reported in some of the animal studies. Key animal studies on lead-induced renal toxicity will be discussed below. 

Renal toxicity induced by penicillamine is usually manifested as reversible proteinuria and hematuria, but may progress to nephrouritic syndrome with membraneous glomerulopathy. 

I 12. The answer is b. (Hardman, pp 1264-1265J Dactinomycin s major toxicities include stomatitis, alopecia, and bone marrow depression. Bleomycin s toxicities include edema of the hands, alopecia, and stomatitis. Mitomycin causes marked bone marrow depression, renal toxicity, and interstitial pneumonitis. Plicamycin causes thrombocytopenia, leukopenia, liver toxicity, and hypocalcemia. The latter may be of use in the treatment of hypercalcemia. Doxorubicin causes cardiotoxicity, as well as alopecia and bone marrow depression. The cardiotoxicity has been linked to a lipid peroxidation within cardiac cells. 

Talmage, S.S. and B.T. Walton. 1993. Food chain transfer and potential renal toxicity of mercury to small mammals at a contaminated terrestrial field site. Ecotoxicology 2 243-256. 

Acetaminophen is usually well tolerated, but potentially fatal hepatotoxicity with overdose is well documented. It should be used with caution in patients with liver disease and those who chronically abuse alcohol. Chronic alcohol users (three or more drinks daily) should be warned about an increased risk of liver damage or GI bleeding with acetaminophen. Other individuals do not appear to be at increased risk for GI bleeding. Renal toxicity occurs less frequently than with NSAIDs. 

NSAIDs are modestly effective for reducing the frequency, severity, and duration of migraine attacks, but potential GI and renal toxicity limit daily or prolonged use. 

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