Diffractaic acid, a novel proapoptotic agent, induces with olive oil both apoptosis and antioxidative systems in Ti-implanted rabbits.

Usnea longissima Ach., a lichen species, is a traditional herbal medicine with anti-detrimental effects. We evaluated the in vivo effects of a major constituent of U. longissima, diffractaic acid, and the main fatty component of the Mediterranean diet, olive oil, against apoptosis, including various caspase activations and oxidative injury in surrounding tissues after titanium implantation in rabbit femurs. Furthermore, we evaluated the underlying molecular mechanisms. In this study, this lichen metabolite and olive oil activated caspase-dependent cell death with apoptotic morphology, which is distinctly different from necrosis. Both orally and locally administered olive oil and diffractaic acid exerted pro-apoptotic induction in tissues surrounding the implants in titanium-implanted rabbits through the activation of initiator caspases (Cas-2, -8 and -9) and executioner caspase (Cas-3). In addition, they displayed strong myeloperoxidase and inducible nitric oxide synthase activities, providing an alleviating effect. Furthermore, administrations of diffractaic acid and olive oil attenuated the Ti-alloy implantation, and decreased superoxide dismutase activity and total glutathione level in peri-implant tissues. These results demonstrate that diffractaic acid and olive oil are involved in the induction of apoptotic cell death both through caspase-dependent cell death and as an antioxidant. Thus, the data suggest that both diffractaic acid and olive oil could be developed as effective proapoptotic agents in various disorders treatments.

Vitamin E and L-carnitine, separately or in combination, in the prevention of radiation-induced brain and retinal damages.

Our aim was to determine the effects of vitamin E and L-carnitine supplementation, individually or in combination, on radiation-induced brain and retinal damages in a rat model. Group 1 received no treatment (control arm). Group 2 received a total dose of 15 Gy external radiotherapy (RT) to whole brain by Cobalt-60 teletherapy machine. Groups 3, 4, and 5 received irradiation plus 40 kg(-1) day(-1) Vitamin E or 200 mg kg(-1)day(-1) L-carnitine alone or in combination. Brain and retinal damages were histopathologically evaluated by two independent pathologists. Antioxidant enzyme levels were also measured. Radiation significantly increased brain and retinal damages. A significant increase in malondialdehyde levels as well as a decrease in superoxide dismutase and catalase enzymes in brain was found in group 2. Separate administration of Vitamin E+RT and L-carnitine+RT significantly reduced the severity of brain and retinal damages and decreased the malondialdehyde levels and increased the activity of superoxide dismutase and catalase enzymes in the brain. The findings of current study support the antioxidant and radioprotective roles of vitamin E and L-carnitine. However, the combined use of Vitamin E and L-carnitine plus irradiation interestingly did not exhibit an additive radioprotective effect.

Vitamin E and L-carnitine, separately or in combination, in the prevention of radiation-induced oral mucositis and myelosuppression: a controlled study in a rat model.

The aim of this study was to determine the effects of vitamin E (VE) and L-carnitine (LC) supplementation, separately or in combination, on radiation-induced oral mucositis and myelosuppression. Group 1 received no treatment (control). Group 2 received 15 Gray of 60Co gamma irradiation as a single dose to total cranium (IR). Group 3, 4, and 5 received irradiation plus 40 mg/kg/day VE (IR+VE) or 200 mg/kg/day LC (IR+LC) or in combination (IR+VE+LC) respectively. Clinically and histopathologically, assessments of mucosal reactions were performed by two independent experts in Radiation Oncology and Pathology, respectively. Hematologic analyses and antioxidant enzyme evaluations were also performed. Irradiation significantly increased oral mucositis, and decreased thrombocyte and White Blood Cell counts. A significant increase in malondialdehyde (MDA) levels and decrease in superoxide dismutase (SOD) and catalase (CAT) activities in plasma were found in the IR group. VE and LC administration, separately, plus irradiation significantly delayed the starting day, and reduced the severity of, oral mucositis. This administration also reduced a fall in the numbers of thrombocyte and WBC caused by irradiation, and decreased the MDA level, and increased the activity of SOD and CAT enzymes in the plasma. VE and LC, in combination, plus irradiation did not provide a superior radioprotection against radiation-induced toxicities.

The effect of zinc sulphate in the prevention of radiation-induced dermatitis.

There is currently substantial clinical interest in zinc (Zn) as a protective agent against radiation-related normal tissue injury. To further assess this drug's potential, the effect of Zn was studied in rats using a radiation-induced skin injury model. Sprague-Dawley rats were divided into four groups. Group 1 received neither Zn nor irradiation (control group). Group 2 received 30 Gy of gamma irradiation as a single dose to the right hind legs of the rats (RT Group). Groups 3 and 4 received the same irradiation plus 5 mg/kg/day Zn (RT+5 Zn group) or 10 mg/kg/day Zn orally (RT+10 Zn group), respectively. The rats were irradiated using a cobalt-60 teletherapy unit. Acute skin reactions were assessed every three days by two independent radiation oncology experts. At the endpoint of the study, light-microscopic findings were assessed by two independent expert pathology physicians. Clinically and histopathologically, irradiation increased dermatitis when compared with the control group (p < 0.05). The severity of radiodermatitis of the rats in the RT+5 Zn and RT+10 Zn groups was significantly lower than in the RT group (p < 0.05); radiodermatitis was seen earlier in the RT group than in the other groups (p < 0.05). Zn was found to be efficacious in preventing epidermal atrophy, dermal degeneration such as edema and collagen fiber loss, and hair follicle atrophy. The most protection for radiation dermatitis was observed in the RT+10 Zn group. It would be worthwhile studying the effects of zinc sulphate supplements in radiation-treated cancer patients, in the hope of reducing radiation-induced toxicity.