Studies on chemical protectors against radiation. XXIX. Protective effects of methanol extracts of various Chinese traditional medicines on skin injury induced by X-irradiation

In order to investigate useful protective medicines for the relief of skin injury induced by irradiation, 60 methanol extracts of Chinese traditional medicines were used in the test of protective potency on skin injury. ICR male mice at 6 weeks of age were whole-body irradiated with 1100R by using a soft X-ray generator (30 kVp, 10 mA, 190 R/min). Each methanol extract of these medicines was injected intraperitoneally into mice before or after irradiation. The degrees of skin injury were determined by a score system of skin reaction within the observation period from 21st to 40th day after irradiation. Protective potency of each medicine on skin injury was calculated from the maximum mean scores of administrated group and un-administrated group. As a result of these studies, the protective potency was detected in Unsei-in, Kumibinro-to, Keisi-syakuyaku-chimo-to, Keigai-rengyo-to, Gosyuyu-to, Koso-san, Saiko-seikan-to, Syo-kankyo-to, Syo-saiko-to, Syoma-kakkon-to, Sen-kan-meimoku-to, Zokumei-to, Sokei-kakketu-to, Bokuryo-in, Mao-to and Rikkunsi-to by intraperitoneal injection before irradiation. Of these effective medicines, only Unsei-in and Mao-to are shown to have a significant protective effect by intraperitoneal injection after irradiation.     

Studies on chemical protectors against radiation. XXXIII. Protective mechanisms of various compounds against skin injury induced by radiation

The radiation protective mechanisms on skin injury induced by soft X-irradiation were investigated by use of various radiation protective agents such as sulfur compounds (MEA, MEG, thiourea), nucleic acid constitutional compounds (adenosine, inosine), antioxidative compounds (sesamol, ferulic acid, ascorbic acid), crude drugs (Rosae Fructus, Anemarrhenae Rhizoma, Trapae Fructus, Forsythiae Fructus, Aloe arborescens). Scavenge action of activated oxygen, inhibitory effect of lipid peroxidation, induction of antioxidative protein and protective effect against damage of deoxyribonucleic acid and superoxide dismutase by X-irradiation were evaluated as the radiation protective mechanisms, and relationship between these results and protective effect of skin injury induced by radiation was studied.     

Studies on chemical protectors against radiation. XXXII. Protective effects of methanol extracts of various Taiwan crude drugs on radiation injuries

This study is to investigate radioprotective effects of 23 Taiwan crude drugs on X-ray induced bone marrow death and skin injury in mice. Each methanol extract of these Taiwan crude drugs was injected intraperitoneally into ICR male mice at 6 weeks of age before irradiation. Mice were whole-body irradiated with a soft X-ray generator. Radiation factors of the two screening tests used were as follows: 70 kVp, 10 mA, 10 mm acrylate filter, 70R/min, 2100R for survival test, and 30 kVp, 10 mA, 190R/min, 1100R for protective test on skin injury. As a result of these studies, the survival effect was recognized in Solani Incani Herba and Orthosiphi Aristati Herba. On the other hand, Mimosae Herba, Canarii Radix, Bombacis Radix, Arecae Fructus, Hedyotidis Diffusae Herba and Cynomorii Caulis were shown to have significant protective potency on skin injury.     

Studies on chemical protectors against radiation. XXXI. Protection effects of Aloe arborescens on skin injury induced by X-irradiation

Protective effects of Aloe arborescens (AA) on mouse skin injury induced by soft X-irradiation were examined. The mechanisms on radiation protection by measuring scavenge activity of activated oxygen, protective effects of nucleic acid, induction of antioxidative protein and so on were further investigated. Consequently a significant protective effect of skin injury was observed in AA S6-3-b. As the mechanisms of radiation protection in AA, the following matters were found. AA S6-3-b showed scavenge activity of hydroxyl radicals generated by Haber-Weiss reaction. AA S6-3-b suppressed the changes of activity in superoxide dismutase and glutathione peroxidase at 7d after soft X-irradiation. Metallothionein was induced in the skin and liver against normal mice at 24 h after administration of AA S6-3-b.     

Studies on chemical protectors against radiation. XXVIII. Protective effect of nucleic acid constitutional compounds on radiation damages induced by X-irradiation

The effects of various nucleic acid constitutional compounds, base, nucleoside and nucleotide on lethality and skin injury induced by soft X-irradiation were studied. The survival effect was determined by use of survival days after irradiation of lethal dose of 70 kVp, 2100R and the protective effect on skin injury was determined by use of degrees on skin injury after 30 kVp, 1100R soft X-irradiation. As a result of these studies, the survival effect was observed by single injection of inosine at 120, 60 and 5 min before irradiation and three times injection after irradiation. And the other nucleic acid constitutional compounds had no effect on survival. Protective effect of skin injury was observed by single injection of adenosine, guanosine, inosine, 5'-adenosine monophosphate (5'-AMP), 5'-guanosine monophosphate (5'-GMP) and 5'-inosine monophosphate (5'-IMP) before irradiation. Protective effect of skin injury by three time injection before irradiation were revealed in adenosine, inosine, 5'-AMP and 5'-IMP. For the investigation of superoxide anions and hydroxyl radicals scavenge activities, the relationship between radical scavenge activities and protective effect of radiation by using various nucleosides was not observed.     

Studies on chemical protectors against radiation. XXVII. Survival effects of methanol extracts of various Chinese traditional medicines on radiation injury

The survival effect of mice irradiated with a lethal dose of X-ray was studied by use of 60 kinds of Chinese traditional medicines. Methanol extracts of these medicines were prepared, and then each extract injected intraperitoneally into male mice before or after whole-body irradiation. As a result of these studies, the survival effects with Ogi-kentyu-to, Simotu-to, Sessyo-in, Zokumei-to and Boi-ogi-to were observed by intraperitoneal injection before irradiation. Of these effective methanol extracts, only Zokumei-to was shown to have a significant survival effect by intraperitoneal injection after irradiation.     

Studies on chemical protectors against radiation. XXXIV. Survival effects of aqueous extracts of various Chinese traditional medicines on radiation injury

In order to develop a nontoxic radioprotector, 60 kinds of Chinese traditional medicines were chosen, and their aqueous extracts tested for their survival effects against the lethal effect of X-irradiation in mice. Radiation factors used were as follows: soft X-rays, 2100R (5.418 x 10(-1) Ckg-1), 70 kVp, 10 mA, 10 mm acrylic filter, 70R (1.806 x 10(-2) Ckg-1)/min. Among 60 medicines tested by intraperitoneal injection immediately before the irradiation, 15 are shown to have the significant survival effect. These 15 effective medicines were also tested by intraperitoneal injection after the irradiation, and the survival effect was recognized in Keisi-syakuyaku-chimo-to, Keigai-rengyo-to, Simotu-to, Syakuyaku-kanzo-to and Hange-syasin-to. On the other hand, the survival effects of 25 medicines including the above-mentioned 15 medicines were investigated by the oral administration at various times before or after the irradiation. As the result of these studies, only Keigai-rengyo-to and Bukuryo-in are shown to have the significant survival effect when administered 2 h before the irradiation.     

Protective effects of various methanol extracts of crude drugs on experimental hepatic injury induced by alpha-naphthylisothiocyanate in rats

Sixty seven methanol extracts of crude drugs were examined for their effects to protect hepatic injury induced by alpha-naphthylisothiocyanate (ANIT) in rats. In terms of the release of intrahepatic enzymes and bilirubin into the serum, 19 extracts were found to suppress the increase in the concentration of serum bilirubin by ANIT. Out of the 19 extracts those of Berchemia Racemosa Caulis, Aurantii Nobilis Pericarpium, Polygoni Avicularis Herba and Gentianae Scabrae Radix, also inhibited the release of several intrahepatic enzymes used as parenchymal injury parameter.     

Protective effects of various methanol extracts of crude drugs on experimental hepatic injury induced by carbon tetrachloride in rats

The protective effects of 67 methanol extracts of crude drugs on rat hepatic injury by carbon tetrachloride (CC14) were examined. In terms of the release of intrahepatic enzymes and bilirubin into the blood, 11 methanol extracts decreased these factors significantly. Among them methanol extracts of Caryophylli Flos, Angelicae Dahuricae Radix, Polygoni Avicularis Herba, Myricae Cortex and Forsythiae Fructus were newly found to have protective effects against acute hepatic injury induced by CCl4. And then these 11 extracts which protected hepatic injury by CCl4 were investigated for their membrane stabilizing and inhibitory effects of lipid peroxidation. The extract of Bupleuri Radix only decreased the hemolysis induced by hypotonic pressure. Nine kinds of extracts without those of Desmodii Herba and Bupleuri Radix suppressed the lipid peroxidation induced by CCl4 in rat hepatic microsomes. In addition, Scutellariae Radix, Caryophylli Flos and Myricae Cortex were shown to have inhibitory effects of non-enzymatic lipid peroxidation in rat hepatic mitochondria. This study reports that the methanol extracts of Caryophylli Flos, Angelicae Dahuricae Radix, Polygoni Avicularis Herba, Myricae Cortex and Forsythiae Fructus protect the hepatic injury by CC14 and these protective effects are connected with the inhibitory effects of the lipid peroxidation in hepatic microsomes.     

Studies on chemical protectors against radiation. XXX. Radioprotective substances of cnidii rhizoma

Radiation protective effects of the methanol extract and its fractions of Cnidii Rhizoma on lethality and skin injury induced by X-irradiation were studied. As a result of these studies, it was observed that significant protective effects exist in both ether and water soluble portions prepared from the above methanol extract, and two of the active principles in the ether and water soluble ones were identified as ferulic acid and adenosine, respectively.     

Protective effect of diethyldithiocarbamate and carbon disulfide against liver injury induced by various hepatotoxic agents

Diethyldithiocarbamate (DTC) and carbon disulfide (CS2), at nearly equimolar oral dose levels, protected mice against liver damage induced by carbon tetrachloride, chloroform, bromotrichloromethane, thioacetamide, bromobenzene, furosemide, acetaminophen, dimethylnitrosamine and trichloroethylene, as evidenced by the suppression of elevations in plasma GPT activity and liver calcium content, and of histopathological alterations. Both agents also prolonged hexobarbital sleeping time and zoxazolamine paralysis time in mice. DTC and SC, alone, given orally, decreased microsomal metabolism of several substrates (aniline, p-nitroanisole, hexobarbital, zoxazolamine, aminopyrine and 3,4-benzopyrene), CC14-induced lipid peroxidation, and cytochrome P-450 content. The loss of microsomal drug-metabolizing enzyme activity was also observed in the experiments in vitro using liver slices and isolated microsomes. Since a characteristic common to such diverse hepatotoxins is that they require metabolic activation before exhibiting hepatotoxicity, the protective mechanisms of DTC and CS2 may involve their interference with the process of metabolic activation of these hepatotoxins. The protective action of DTC may be mediated almost entirely through CS2 when administered orally and at least partly with parenteral administration, since, in CCl4-induced liver injury, DTC was most effective when given orally, while the action of CS2 was less dependent on the route of administration. Thus CS2 and CS2-producing agents in vivo such as dithiocarbamate derivatives and disulfiram may modify toxicological and pharmacological effects of foreign compounds by inhibiting microsomal drug-metabolizing enzyme activity in the liver.