Radiation‐induced lymphoid tumors and radiation lethality are inhibited by combined treatment with small doses of zinc aspartate and wr 2721

Abstract

Combined small doses of zinc aspartate and WR 2721 provided additive protection against radiation lethality in mice. Survival obtained with a small dose of WR 2721 which was ineffective alone could be enhanced to 83% by combining the drug with zinc aspartate, which on its own also displayed no effect. The survival of 25% provided by a higher dose of WR 2721 was increased significantly by adding zinc aspartate. Additivity was also tested in a model of radiation carcinogenesis. For this purpose, lethality and occurrence of lymphoid tumors induced by fractionated total-body irradiation were studied in C57B1/6 mice treated with zinc aspartate and WR 2721. In order to reveal additive effects, both agents were used at sub-optimal dosages. In mice subjected to 5 daily exposures of 1.9 Gy, the combination of zinc aspartate and WR 2721 was effective and enhanced the survival to 83% as compared with 25% afforded by WR 2721 alone (p < 0.005). Similarly, histological assessment of organ involvement with lymphoma revealed that zinc aspartate and WR 2721 alone did not bring about a significant reduction of lymphoma incidence. On the other hand, the combined agents diminished organ involvement with lymphoma to 9.1% as against 90% in the controls (p < 0.0005) and 62.5% with WR 2721 alone (p < 0.025). Thus, combined treatment with zinc aspartate and WR 2721 also inhibited radiation-induced lymphoid tumors.

Histopathological and Histochemical Assessment of the Protective Effects of Zinc on Ethanol-Induced Acute Hepatotoxicity in Adult Albino Rats

“…This also might be explained according to the ethanol-induced metabolic failure especially to ATP production which directs the switch in pathway to apoptosis or necrosis as reported by a previous study [58]. Furthermore, the results of the present study were parallel to some previous authors who studied apoptosis and the protective effects of zinc against forebrain ischemia [59], sporidesmininduced apoptosis in macrophages and T lymphoblasts [60], cadmiuminduced hepatotoxicity and nephrotoxicity [61] and even against radiation lethality in mice [62].…”

Metallothionein 1G and Zinc Sensitize Human Colorectal Cancer Cells to Chemotherapy

“…Interestingly, zinc by itself has been shown in xenograft models to be an effective antitumoral agent (36,37), as well as being implicated in the mechanism of action of novel therapies (38)(39)(40)(41). There are multiple studies suggesting that zinc addition to chemotherapeutic agents improves their antitumoral capacity, in xenograft models (20,42) as wells as in humans (43,44), and against chemoresistant cells (45).…”

Zinc in innate and adaptive tumor immunity

“…In several studies, zinc-supplemented animals have increased resistance to apoptotic inducers. For example, zinc has protective effects against whole body irradiation in mice [145], neuronal apoptosis following transient forebrain ischemia in the hippocampus of primates [146], and apoptosis of the anterior and stromal keratinocytes in the eye following superficial keratectomy in rabbits [147]. PBLs pretreated with zinc are resistant to Cr(III)(phe)3 induced apoptosis.…”