Changes in endogenous tissue glutathione level in relation to murine ascites tumor growth and the anticancer activity of cisplatin

Abstract

Changes in glutathione levels were determined in tissues of 11-to 12-week-old Swiss albino mice at different stages of Daltons lymphoma tumor growth and following cisplatin (8 mg/kg body weight, ip) treatment for 24-96 h, keeping 4-5 animals in each experimental group. Glutathione levels increased in spleen of tumor-bearing compared to normal mice (9.95 ± 0.14 vs 7.86 ± 1.64 µmol/g wet weight, P£0.05) but decreased in blood (0.64 ± 0.10 vs 0.85 ± 0.09 mg/ml) and testes (9.28 ± 0.15 vs 10.16 ± 0.28 µmol/g wet weight, P£0.05). Daltons lymphoma cells showed an increase in glutathione concentration (4.43 ± 0.26 µmol/g wet weight) as compared to splenocytes, their normal counterpart (3.62 ± 0.41 µmol/g wet weight). With the progression of tumor in mice, glutathione levels decreased significantly in testes (~10%) and bone marrow cells (~13%) while they increased in Daltons lymphoma cells (28-46%) and spleen (15-27%). Glutathione levels in kidney, Daltons lymphoma cells and bone marrow cells (8.50 ± 1.22, 4.43 ± 0.26 and 3.28 ± 0.17 µmol/g wet weight, respectively) decreased significantly (6.04 ± 0.42, 3.51 ± 0.32 and 2.17 ± 0.14 µmol/g wet weight, P£0.05) after in vivo cisplatin treatment for 24 h. Along with a decrease in glutathione level, the glutathione-S-transferase (GST) activity also decreased by 60% in tumor cells after cisplatin treatment. The elevated drug uptake by the tumor cells under the conditions of reduced glutathione concentration and GST activity after treatment could be an important contributory factor to cisplatins anticancer activity leading to tumor regression. Furthermore, lower doses of cisplatin in combination with buthionine sulfoximine (an inhibitor of glutathione synthesis) may be useful in cancer chemotherapy with decreased toxicity in the host. Correspondence

Changes in oxidative stress intensity in blood of tumor-bearing rats following different modes of administration of rhenium-platinum system

“…Administration of cPt did not affect the enzyme activity compared to the tumor-bearing rats, despite a significant antitumor effect of cPt. Since, GP is glutathione-dependent enzyme, it should be noted that cPt directly interacts with glutathione [23] and binds specifically with selen and thiol groups at the GP active center [13] that results in the enzyme inactivation. Probably, that is why the level of the GP activity did not increase, although a significant inhibition of tumor growth was observed.…”

Impacto da suplementação de vitamina C sobre níveis de peroxidação lipídica e glutationa reduzida em tecido hepático de camundongos com imunossupressão induzida por ciclofosfamida

“…Uma elevação intracelular em seus níveis tem sido atribuída à resistência das células cancerosas ao estresse oxidativo, radioterapia e quimioterapia, enquanto que uma depleção dos mesmos poderia aumentar a citotoxicidade de uma variedade de agentes antitumorais 28,29 .…”

Neuroprotective Activity of Valeriana officinalis against Global Cerebral Ischemia/Reperfusion Induced Oxidative Stress in Rat

“…The supernatant was again centrifuged at 15000 rpm for 1 h at 4°C. The supernatant obtained was used for further estimation of superoxide dismutase (SOD), 14 catalase (CAT), 15 glutathione (GSH) 16 and total thiols 17 .…”