Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since carboplatin (CBDCA) is a platinum compound of second generation, its ototoxicity was investigated. In order to assess the ototoxicity, hearing acuity was measured based on the compound action potential (AP), and the organ of Corti was morphologically studied using scanning electron microscopy (SEM) and succinate dehydrogenase (SDH) staining in guinea pigs treated with CBDCA. CBDCA induced morphological changes in the organ of Corti when the guinea pigs received 50 mg/kg daily for 2 or 3 days. The threshold value of AP was elevated 10 to 25 dB in treated animals, as compared with the control value. The SEM study and SDH staining revealed that the administration caused scattered degeneration of the outer hair cells (OHCs), and the inner hair cells remained intact. These lesions were milder than those of OHCs treated with cisplatin (CDDP). The rapid elimination of CBDCA from the kidney and the inner ear seems to account for the low ototoxicity of this compound. Although CBDCA is less toxic than CDDP, it may affect hearing function if patients suffer from renal dysfunction or if the organ of Corti is vulnerable.
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PMID:Ototoxicity of carboplatin in guinea pigs. 247 98

The chemosensitivities of 77 samples of human head and neck cancer were examined by in vitro succinate dehydrogenase inhibition (SDI) test. The tumor tissues obtained at biopsy specimens were exposed to doxorubicin (DXR) and pirarubicin (THP). The average decrease of the enzyme activity by THP was significantly greater than that by DXR. In 60 cases of squamous cell carcinomas, the chemosensitivity of poorly differentiated type tended to be higher compared to the well differentiated type. It is suggested from there results that THP is a more effective anticancer drug than DXR against human head and neck cancers. Clinically good responses were obtained in a systemic chemotherapy of such as head and neck adenoid cystic carcinomas by combining THP with other anticancer drugs such as CDDP (or CBDCA) and CPA.
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PMID:[Basic and clinical evaluation of the effect of pirarubicin against head and neck cancer--chemosensitivity test and a comparative study with doxorubicin]. 815 89

Carboplatin preferentially destroys inner hair cells (IHCs) and type-I spiral ganglion neurons while sparing outer hair cells (OHCs). Loss of IHCs and type-I ganglion cells is associated with a significant reduction of the compound action potential (CAP). However, the cochlear microphonic (CM) potential and distortion product otoacoustic emissions (DPOAEs) remain normal, indicating that the OHCs are functionally intact. In the vestibular system, carboplatin selectively destroys type-I hair cells and their afferent neurons. Damage of type-I vestibular hair cells and their afferent terminals is associated with significant depression of nystagmus induced by cold, caloric stimulation. Histochemical studies revealed a rapid decrease in succinate dehydrogenase (SDH) staining in IHCs soon after carboplatin treatment, and staining intensity remained depressed in surviving IHCs for at least 1 month after carboplatin treatment. These results suggest that carboplatin depresses the metabolic function in surviving IHCs. Several lines of evidence suggest that free radicals may contribute to carboplatin-induced sensory cell damage. Intracochlear infusion of L-buthionine-[S,R]-sulfoximine (BSO), which depletes intracellular glutathione (GSH), increases IHC and OHC loss. Previous in vitro studies have shown that neurotrophin 4/5 (NT-4/5) promotes the survival of spiral ganglion neurons from cisplatin ototoxicity. In vivo perfusion of NT-4/5 promoted the survival of spiral ganglion neurons, but did not protect the hair cells.
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PMID:Selective loss of inner hair cells and type-I ganglion neurons in carboplatin-treated chinchillas. Mechanisms of damage and protection. 1084 92

In an attempts to increase the antitumor effect and to reduce normal tissue toxicity, the combined cytotoxic effect of cis-Diamminedichloroplatinum (II) (CDDP) and cis-diammine(1,1-cyclobutane dicarboxylate) platinum (II) (CBDCA) was investigated using HeLa and colon 26 cell lines and the combination index (CI). Cytotoxicity of the combination of CDDP and CBDCA on 27 surgically resected specimens of human gastric and colorectal adenocarcinomas was also evaluated using the in vitro succinate dehydrogenase inhibition (SDI) test. The CI values varied with the dose ratio examined (1:1-1:6) of CDDP and CBDCA, with findings that CI<1, synergy, was obtained at fraction affected (Fa)>0.75 for HeLa cells and at Fa<0.9 for colon 26 cells in cases of a dose ratio of 1:1 to 1:2. Of all 27 clinical human adenocarcinomas, the succinate dehydrogenase (SD) activity was significantly lower in cancer cells concomitantly exposed to both CDDP and CBDCA than in those exposed to either drug alone. These positive effects of a combination of two platinum analogues on human malignant tissues have heretofore not been reported, which would warrant the clinical application of this combination for human malignant tumors.
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PMID:Synergism of cytotoxicity between cis-diaminedichloro-platinum-(ii) and cis-diamine(1,1-cyclobutanedicarboxylate)-platinum-(ii). 2156 28