Several clinically used sulfur-containing compounds were examined as potential antagonists for the nephrotoxicity of cisplatin in Sprague-Dawley rats. The compounds studied were biotin, captopril, cefoxitin, cephalexin, the sodium salt of penicillin G, sulfathiazole, and thiamine hydrochloride. Biotin, captopril, cephalexin, and sulfathiazole were found to have a significant effect in reducing the nephrotoxicity of cisplatin when administered simultaneously with cisplatin via an intravenous route in the rat. Biotin was the most effective in providing renal protection and sulfathiazole the least effective, based upon BUN, serum creatinine values, and weight changes, though all four of these compounds provided a considerable measure of protection against the typical cisplatin-induced nephrotoxicity. The effect of the simultaneous administration of cisplatin with biotin, cephalexin, and sulfathiazole was examined on the antitumor activity of cisplatin toward the L1210 murine leukemia in the DBA/2 mouse and the Walker 256 carcinosarcoma in the rat. With the L1210 murine leukemia no loss of antitumor activity was found for any of the compounds. With the Walker 256 carcinosarcoma some loss of antitumor activity was found with biotin. Both biotin and sulfathiazole are shown to be promising candidates for use in the suppression of the adverse effects of cisplatin, and other sulfur-containing compounds currently in clinical use may have equivalent or superior properties in this respect.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDesign of in vivo Cadmium-Mobilizing Agents: Synthesis and Properties of Monobenzyl meso-2,3-DimercaptosuccinateMark M. Jones, Pramod K. Singh, Mark A. Basinger, Glen R. Gale, Alayne B. Smith, and Wesley R. HarrisCite this: Chem. Res. Toxicol. 1994, 7, 3, 367–373Publication Date (Print):May 1, 1994Publication History Published online1 May 2002Published inissue 1 May 1994https://pubs.acs.org/doi/10.1021/tx00039a014https://doi.org/10.1021/tx00039a014research-articleACS PublicationsRequest reuse permissionsArticle Views125Altmetric-Citations7LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Silver-dollar plant is a new state record. A native of southeastern Europe, this species is commonly cultivated and is occasionally escaped from cultivation. Swink and Wilhelm (1994) report that this species is “rather frequent in the eastern sector” of the Chicago region. In the United States, this species has been collected in 25 states from Maine west to Minnesota and south to Arkansas and Georgia in the east and from Washington south to California and east to Nevada in the west (USDA, NRCS 1999). Plants are coarse annuals or biennials to 1 m tall with opposite or subopposite, cordate basal leaves, alternate cauline leaves, flowers with large purple petals, cordate basal leaves, and broadly elliptic silicles with silvery septa are diagnostic characteristics (Bailey 1940, Fernald 1950, Mohlenbrock 1986, Gleason and Cronquist 1991).
Plasma atrial natriuretic peptide (ANP) concentrations were monitored in two experimental models of protection from cisplatin nephrotoxicity. Sprague-Dawley rats made diabetic with streptozotocin (65 mg/kg) were protected from cisplatin-induced nephrotoxicity when compared to control rats as indicated by reduced plasma creatinine (0.49 +/- 0.02 vs. 0.9 +/- 0.06 mg/dl; P less than .001) and blood urea nitrogen concentrations (18.51 +/- 1.4 vs. 43.08 +/- 2.1 mg/dl; P less than .001). Plasma ANP was also increased with experimental diabetes (76.5 +/- 8.98 fmol/ml) vs. normoglycemic controls (43.8 +/- 8.9 fmol/ml; P less than .02). When diabetic rats were treated with insulin, the renal protection observed with the diabetic state was reversed (creatinine, 0.70 +/- .05 mg/dl); plasma ANP concentrations were also reduced (52.2 +/- 15.2 fmol/ml). Renal platinum concentrations were significantly lower in the diabetic group and the reversal of diabetic-induced renal protection with insulin was associated with increased renal platinum concentrations. In rats given a single i.p. dose of cisplatin (5 mg/kg), a reduction in cisplatin-induced nephrotoxicity was observed when 5% NaCl was the vehicle of choice compared to that seen in rats given the same dose of drug in 0.9% saline (creatinine, 0.43 +/- 0.07 with 5% NaCl vs. 0.63 +/- 0.03 with 0.09% NaCl). NaCl (5%) administration also resulted in increased plasma ANP concentrations when compared to rats receiving equivalent volumes of 0.9% NaCl (88.4 +/- 6.2 vs. 50.5 +/- 5.6 fmol/ml, respectively). These data suggest that increased endogenous ANP may be a mechanism of renal protection common to both experimental diabetes and hypertonic saline administration. Chronically increased ANP may prevent renal accumulation of platinum in the kidney.
The dithiocarbamate enhancement of the biliary excretion of cadmium in rats loaded with cadmium (by either the oral or sc route) was found to be strongly dependent on the structure of the groups attached to the nitrogen atom of the dithiocarbamate moiety. Those dithiocarbamates containing hydroxyl‐bearing attached groups were found to be capable of causing the greatest enhancement of the cadmium content of the bile. For the compounds of this type that were examined, this enhancement of biliary cadmium content varied from 30‐fold to over 2000‐fold. No enhancement of the biliary excretion of cadmium was found subsequent to the administration of sodium diethyldithiocarbamate, though this compound is known to cause a significant increase in the fecal excretion of cadmium.
Silene ovata is a perennial species in the pink family characterized by cauline leaves that are ovate and clasping and flowers with deeply notched petals, each petal often with 8 segments. This species is state endangered and only occurs in Hardin County in extreme southeast Illinois. Five populations were surveyed twice in 1998 and a sixth population was surveyed once in 2000. A total of 3612 plants were sampled, with 93% of the plants in two populations. Plants tended to be multi-stemmed. Over one-half of the plants that were surveyed in June 1998 flowered the following September, but capsules were only produced at the Sturgeon Hill population. The most consistent features of the habitat were upland forest of varying moisture regimes, moderate to steep slopes, often very rocky with cliffs and slide blocks common, shallow loess-derived soils above sandstone rock, and a soil pH between 5.8 and 6.2.
The effects of two dithiocarbamates (both of which induce an increase in the excretion of cadmium) on the biliary and urinary excretion of the essential trace elements zinc, copper, iron, magnesium, and calcium have been examined in the female Sprague-Dawley rat to estimate what alterations in the excretion of essential metals accompanies the use of these compounds. The dithiocarbamates studied were sodium diethyldithiocarbamate (DDTC) and sodium N-(4-methylbenzyl)-4-O-(β-D-galactopyranosyl)-D-glucamine-N-carbodithioate (MeBLDTC). DDTC induced a modest decrease in the biliary and urinary excretion of copper. The biliary excretion of both zinc and iron was significantly enhanced when MeBLDTC was given ip to normal rats, while those of copper, magnesium, and calcium were not significantly affected by this compound. DDTC treatment of normal female rats which had not been administered cadmium resulted in a slight decrease in the iron level of the liver. Treatment of rats with cadmium chloride resulted in a significant increase in the zinc and iron levels of the kidney, liver, and pancreas and an increase in the copper levels of the kidney and the liver. After a treatment with MeBLDTC, which reduced hepatic cadmium levels, only some of the levels of these essential metals were modified toward the levels found in untreated controls. Cadmium-loaded animals from which hepatic cadmium had been mobilized by MeBLDTC did not differ in renal or hepatic histopathology from the control (untreated) animals or from the group which had received cadmium only.
A phase II trial was conducted with 15 patients (mean age of 65.7 years) with locally recurrent or intransit melanoma of the extremities. After total outflow occlusion with pneumatic tourniquet, the cell-cycle nonspecific anti-neoplastic agent cis-diamminedicholoroplatinum (CDDP) was infused intra-arterially in a mean dose of 26.7 mg/m2 per infusion (2.6 infusions per patient). The aim of this study was to determine the efficacy of CDDP infusion for control of intransit and recurrent melanoma of the extremities. Three to four weeks postinfusion, all visible residual disease was resected. Partial remissions were observed in ten patients (67%); five patients achieved stable disease status. No patient had complete regression of disease. At an average follow-up interval of 18.3 months (range 4-44 months), the mean local/regional disease-free survival was 14.8 months. Eighty per cent of patients (twelve of 15) had local/regional control of disease at an average follow-up of 14.8 months after CDDP infusion and surgical resection. Of five melanoma-related deaths, three patients had had no local/regional recurrence at the time of their demise. Three compartment syndromes resulted as a complication of the infusional therapy and occurred within 1-3 days of the treatment. In vitro growth of melanoma from lymph nodes draining the infused area was seen in all subjects studied. Outgrowth from tumor within the tourniquet infusion area was observed in two patients, both of whom experienced recurrences clinically at 24-months' postinfusion. Pharmacokinetic data of total CDDP concentrations from tissue and blood (n = 4) were available from pretreatment to 1 hour post-therapy. Biopsy data from patients pre- and post-treatment suggest substantial tumor uptake of CDDP as compared to local or distal normal skin, with minimal CDDP loss to the systemic circulation. Pharmacologic and clinical data of this phase II trial suggest that intraarterial infusion with tourniquet outflow-occlusion augments tumor tissue levels of CDDP within the infused extremity and enhances local control of high-risk and intransit disease.
