Influence of ionizing radiation on Echis pyramidium snake venom: Biochemical and immunological aspects

The effect of a single LD[50] dose of native Echis pyramidum venom [27.69 micro g/mouse] on the activities of certain serum enzymes levels: aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP], urea, creatinine, lactate dehydrogenase [LDH], creatine phosphokinase [CPK], creatine kinase isoenzyme [CK-MB] were studied. Samples from the serum were collected 4hr following LD50 venom dose intraperitonealy injected in male Swiss albino mice. The activities of these enzymes showed significant elevation compared to the non-envenomated group. In contrast, an equivalent dose of 1.5 kGy gamma irradiated Echis pyramidum venom [27.69 micro g/mouse] did not cause any significant increase compared to non-envenomated group. The effect of a dose that is equivalent to ½ LD[50][13.8 micro g/50 micro l] of native Echis pyramidum venom on plasma creatine phosphokinase [CPK] induced a significant increase of creatine phosphokinase [CPK] level compared to normal control [P<0.01]. In contrast, an equivalent dose of 1.5 kGy gamma irradiated Echis pyramidum venom showed non significant difference in creatine phosphokinase activity when compared to the normal control. Light microscopic examinations of gastrocenemius muscles of mice injected with native Echis pyramidum venom [½ LD[50]; 13.8 micro g/50 micro l] showed fragmentation, disorganization, loss of myofibrils in some of the muscle fibers, hemorrhage in-between the muscle fibers and mononuclear cellular infiltration. While light microscopic examinations of gastrocenemius muscles of mice injected with 1.5 kGy gamma irradiated Echis pyramidum venom [13.8 micro g/50 micro l; a dose identical to that used from native venom] showed that most muscle fibers were of normal appearance except for small area of fragmentation and disorganized myofibrils and oedema of the intercellular connective tissue. Double immunodiffusion test revealed a similar reactivity for native, 1 kGy, 1.5 kGy and 3 kGy gamma irradiated Echis pyramidum venoms against a commercial polyvalent Egyptian antivenin. The visible lines obtained in the immunodiffusion reactions were identical and joined smoothly at the corners, indicating that there was no change in their antigenic reactivity. These results demonstrate that the ability of the venom antigens to react with its corresponding antibodies was maintained in spite of being exposed to radiation doses of 1 kGy, 1.5 kGy and 3 kGy. Both antivenins raised against native or 1.5 kGy gamma irradiated venoms recognized Echis pyramidum venom when submitted to protein blotting, but the anti 1.5 kGy gamma irradiated venom show a higher intensity bands than the antivenin raised against native Echis pyramidum venom, in spite of having less neutralizing activity [native neutralize 50 LD[50], 1.5 kGy gamma irradiated neutralize 40 LD[50]], this indicates that antibodies were formed not only for toxic fraction but also for non toxic fraction. Irradiation of the whole Echis Pyramidium Venom with 1.5KGy reduced its lethality 12.5 times though keeping its immunogenicity. The 1.5KGy dose was shown to be the best radiation dose to promote detoxification without significantly affecting its immunogenicity. Thus results of this study confirm the conclusion that gamma radiation is a suitable way to detoxify Echis Pyramidium Venom without affecting its immunogenicity provided that proper dose is used

Low dose gamma irradiation modifies the effect of L-carnitine, curcumin, garlic powder and green tea extract on doxorubicin-induced nephropathy in rats

The possible protective potential of exposure to low dose of gamma radiation in presence or absence of L-carnitine, curcumin, garlic powder or green tea extract was examined in the present study on doxorubicin [DOX]-induced experimental nephropathy in rats. Preliminary study was carried out to select the suitable dose of DOX to induce nephrotoxicity. In the current experiment 5 mg/kg, i.p. was selected as a single dose to induce nephrotoxicity during 15 days. The possible modulating effect of L-carnitine, curcumin, garlic powder or green tea extract on kidney function was examined. Animals were subdivided into three sets. Three groups of the 1[st] set were exposed to [gamma] radiation at a single dose level of 0.3 Gy then received DOX, 1, 3 or 7 days postirradiation respectively. The groups of 2[nd] set daily received L-carnitine [40 mg/kg, i.p.], curcumin [50 mg/kg, i.p.], garlic powder [100 mg/kg, p.o.] and green tea extract [300 mg/kg, p.o.] daily for two weeks before induction of nephropathy. Groups of the 3[rd] set received the same doses of drugs then were injected with DOX, 1, 3 or 7 days following gamma irradiation respectively. Two groups of animals, one of them received saline and served as normal and the other received DOX and served as nephropathic group were included in 1[st], 2[nd] as well as 3[rd] set. Fifteen days following DOX administration, serum was collected and the animals were then sacrificed. Serum creatinine, urea and uric acid were evaluated. Data revealed that, a single DOX dose [5 mg/kg] induced marked acute nephrotoxicity manifested as significant increase in the activities of serum creatinine, urea as well as uric acid. Interestingly, pre-exposure to gamma radiation at a dose level of 0.3 Gy, 1 or 3 days before DOX injection exhibited significant improvement in the above altered mentioned parameters. However, exposure to low dose radiation 7 days prior to DOX administration did not show a protective effect. Moreover, pretreatment with L-carnitine, curcumin, garlic powder or green tea extract in rats unexposed or exposed to gamma radiation before DOX administration ameliorated, to a great extent, the effects induced by DOX. The present findings suggest that exposure to a single low dose of gamma radiation [0.3 Gy] one day before DOX administration is a promising approach for maximizing the nephroprotective effects of L-carnitine, curcumin, garlic powder or green tea extract with minimal adverse effects of DOX

radioprotective efficiency of combined administration of natural antioxidants [rutin and vitamin e] and a sulfhydryl compound in irradiated rats

In the present study, the radioprotective effects of natural antioxidants, rutin alone, vitamin E alone or both of them combined with a synthetic radioprotector, cysteine, have been investigated in irradiated rats. Furthermore, the oxidative stress biomarkers and certain liver function tests of the whole body irradiated rats were examined. The effect of irradiation was evaluated by exposing the whole body of rats to gamma radiation at acute single dose of 6.5 Gy. Rutin [1.064 mmol/kg] was daily administered orally for two weeks before irradiation, vitamin E [50 mg/100g] was injected intraperitoneally daily for seven days before irradiation, while, cysteine [30 mg/kg] was intra-peritoneally administered 30 mm. only before irradiation. Blood and liver malondialdehyde [MDA], glutathione [GSH] and plasma superoxide dismutase [SOD] levels were evaluated. Serum aspartate aminotransferase [AST], alanine aminotransferase [ALT] and alkaline phosphatase [ALP] activities were also measured in various groups. The data revealed deleterious damage of radiation exposure which was manifested as a significant increase in lipid peroxidation measured as MDA. On the other hand, the activity of SOD and the level of GSH were reduced after irradiation. In addition, the activities of serum ALP, AST and ALT were markedly elevated after radiation exposure. Administration of rutin or vitamin E alone or combined with cysteine before radiation provided a protective effect as measured by the tested parameters. It could be concluded that treatment with the natural antioxidants can control radiation-induced oxidative damage in the biological system. This study indicates that the use of combination of agents is a promising approach for maximizing radioprotection with minimal adverse effects. Administration of cysteine iucreases the radioprotective effects of rutin and vitamin E against the damaging effects of ionizing radiation

Study of the radioprotective efficiency of combined administration of cysteine and natural antioxidants [rutin and vitamin E] in feverish irradiated rats

In the present experiments, a study of the radioprotective effects of natural antioxidants, rutin alone, vitamin E alone or each of them combined with synthetic radioprotector, cysteine, have been investigated in feverish irradiated rats. Furthermore, the oxidative stress biomarkers of the feverish whole body irradiated rats were examined. The data revealed deleterious damage of radiation exposure which was manifested as significant increase in lipid peroxidation measured as malondialdehyde [MDA]. On the other hand, the activity of plasma superoxide dismutase [SOD] and the blood level of glutathione [GSH] were reduced after irradiation. Effect of hyperthermia on oxidative stress biomarkers in rats were studied in this work and data showed that the increase in body temperature intensified lipid peroxidation processes where MDA in plasma and liver homogenate was increased, GSH level in blood and liver homogenate was also increased while plasma SOD activity was reduced. Effect of rutin alone, vitamin E alone or each of them combined with cysteine on oxidative stress biomarkers in hyperthermic irradiated rats was investigated. Results indicated that, pretreatment with vitamin E and rutin alone or combined with cysteine before the onset of hyperthermia significantly attenuated fever-induced increase in free radical formation and lipid peroxidation. Radiation exposure at acute single dose of 6.5 Gy did not change the body temperature when measured on the 3[rd] day following exposure. In order to determine any antipyretic effect of the drugs used, the body temperature of each animal was measured before induction of hyperthermia as well as 18 hours following yeast injection. Rats were treated with the tested drugs before induction of fever then exposed to whole body gamma radiation at acute single dose of 6.5 Gy and body temperature of each animal was measured 3 days after irradiation. Only rutin had an antipyretic effect in yeast-induced hyperthermia in rats

Gamma irradiation of Egyptian cobra [Naja haje] venom

The aim of the present study was to prepare an effective and safe toxoid for the Egyptian Cobra [Naja haje] Venom by gamma irradiation. The effects of gamma irradiation [0.1-10 M rad] on the toxicity, as well as the antigen antibody complex formation reactivity was described. It appears from the results that the lethality of Naja haje venom irradiated in the dry form was not affected up to a dose of 10 M rad [100 KGy]. On the other hand the venom irradiated in the aqueous solution form showed a decrease in its lethality, and this was proportionately related to the dose of irradiation, while the ability of the venom antigens to react with its corresponding antibodies was retained up to irradiation dose of 5 M rad. The results of double immunodiffusion of non irradiated and the different dose levels of gamma irradiated venom [0.1-5 M rad] against a commercial Egyptian poly valent antivenin, all showed similar patterns the four visible lines obtained in the immunodiffusion reactions were identical and joined smoothly at the corners, indicating that there was no change in antigenic reactivity with antibodies determinants