Vascular sclerosing effects of bleomycin on cutaneous veins: a pharmacopathologic study on experimental animals.

BACKGROUND:: Varicose veins and the complications of venous disease are common disorders in humans. OBJECTIVE:: To study the effects of bleomycin as a potential new sclerosing agent and its adverse events in treating varicose veins. METHODS:: Bleomycin-loaded liposomes 0.1ml was injected in the dorsal ear veins of white New Zealand rabbits. Sodium tetradecyl sulfate was used as a positive control. Normal saline was used as negative control. The blood vessels of the treated ears were photographed before and at one hour and two, eight and 45 days after treatment. Biopsies from the treated areas were obtained for histological examination. Blood samples were collected to determine any possible toxicity. RESULTS:: Bleomycin by itself was ineffective; therefore, liposomes were used as a vector to deliver bleomycin to the vein lumen. Subsequently, bleomycin started showing its sclerosing effects. Toxicity monitoring showed no apparent hematologic, pulmonary, hepatic or renal toxicities. This study revealed that bleomycin induced vasculitis, which led to vascular occlusion, which was observed on day 1 and day 8. No bleomycin-related injury was noted by histopathological examination of lung sections. The calculation of the lung/body weight coefficient indicated that edema was present in the experimental groups compared with the negative and positive controls. STUDY LIMITATIONS:: Relatively small number of experimental animals used. CONCLUSIONS:: This study showed that bleomycin-loaded liposomes were able to induce vasculitis and vascular occlusion without any toxicity or complications. It might be useful, hence, to treat patients suffering from Varicose veins and other ectatic vascular diseases with this agent.

Vascular sclerosing effects of bleomycin on cutaneous veins: a pharmacopathologic study on experimental animals

Abstract: Background: Varicose veins and the complications of venous disease are common disorders in humans. Objective: To study the effects of bleomycin as a potential new sclerosing agent and its adverse events in treating varicose veins. Methods: Bleomycin-loaded liposomes 0.1ml was injected in the dorsal ear veins of white New Zealand rabbits. Sodium tetradecyl sulfate was used as a positive control. Normal saline was used as negative control. The blood vessels of the treated ears were photographed before and at one hour and two, eight and 45 days after treatment. Biopsies from the treated areas were obtained for histological examination. Blood samples were collected to determine any possible toxicity. Results: Bleomycin by itself was ineffective; therefore, liposomes were used as a vector to deliver bleomycin to the vein lumen. Subsequently, bleomycin started showing its sclerosing effects. Toxicity monitoring showed no apparent hematologic, pulmonary, hepatic or renal toxicities. This study revealed that bleomycin induced vasculitis, which led to vascular occlusion, which was observed on day 1 and day 8. No bleomycin-related injury was noted by histopathological examination of lung sections. The calculation of the lung/body weight coefficient indicated that edema was present in the experimental groups compared with the negative and positive controls. Study limitations: Relatively small number of experimental animals used. Conclusions: This study showed that bleomycin-loaded liposomes were able to induce vasculitis and vascular occlusion without any toxicity or complications. It might be useful, hence, to treat patients suffering from Varicose veins and other ectatic vascular diseases with this agent.

Ultra-structural effects of different low-level lasers on normal cultured human melanocytes: an in vitro comparative study.

The aim of this study was to investigate the effects of the different types of low-level laser therapy (LLLT) on the ultra-structure and number of melanosomes in normal cultured human melanocytes. Specific effects of various types of LLLT on the ultra-structure of melanosomes have not yet been reported. Melanocytes were exposed to LLLT at an energy level of 2.0 J/cm2, using a blue (457 nm), red (635 nm), or ultraviolet (UV) (355 nm) laser. After 72 h of irradiation, the melanocytes were fixed in 2.5 % glutaraldehyde (pH 7.2) phosphate buffer for 8 h and analyzed by transmission electron microscopy. Four developmental stages (I to IV) of melanosomes were observed, and their numbers were counted manually. The percentage of stages I, II, III, and IV melanosomes was 12.8, 14.2, 22.6, and 50.3 %, respectively, in the control (sham light). However, the melanosome percentages were 41.2, 5.4, 8.2, and 24.2 % in stages I, II, III, and IV, respectively, in the blue laser-treated group; 58.4, 6.1, 9.3, and 26.2 % for stages I, II, III, and IV, respectively, in the red laser-treated group; and 31.3, 11.1, 16.5, and 41.1 % for stages I, II, III, and IV, respectively, in the UV laser-treated group. The present data show that the amount of stage I is significantly higher (P < 0.0001) in the LLLT-treated cells compared to the control, which indicates significant stimulation of melanogenesis. The red laser was more effective than the other lasers. Moreover, the effects of LLLT on the ultra-structure of melanosomes need to be studied in a larger number of subject groups.

Ginger ingredients inhibit the development of diethylnitrosoamine induced premalignant phenotype in rat chemical hepatocarcinogenesis model.

To investigate the possible antitumor activity of ginger extract against hepatic carcinogenesis initiated by diethylnitrosoamines (DEN) and promoted by carbon tetrachloride (CCl(4) ). A total of 60 male Wistar albino rats were divided into four groups with 15 animals in each group. Rats in group 1 (control group) received a single intraperitoneal (i.p.) injection of normal saline. Animals in group 2 were given ginger (50 mg/kg/day) in drinking water for 8 weeks. Rats in group 3 (DEN group) were injected with a single dose of DEN (200 mg/kg, i.p.), 2 weeks later received a single dose of CCl(4) (2 mL/kg i.g) by gavage as 1:1 dilution in corn oil. Animals in group 4 (DEN-ginger group) received the same carcinogenesis induction protocol as in group 3 plus ginger (50 mg/kg/day) in drinking water for 2 weeks before induction of hepatocarcinogenesis and continued throughout the experimental period. DEN-initiated and CCl(4) -promoted hepatocarcinogenesis in male Wistar rats was manifested biochemically by elevation of serum hepatic tumor markers tested; α-fetoprotein and carcinoembryonic antigen. In addition, hepatocarcinogenesis was further confirmed by a significant increase in hepatic tissue growth factors; vascular endothelial growth factor, basic fibroblast growth factor, and hydroxyproline content. A marked decrease in endostatin and metallothonein were also observed. Long-term ginger extract administration 2 weeks before induction of hepatocarcinogenesis and throughout the experimental period prevented the decrease of the hepatic content of metallothionein and endostatin and the increase in the growth factors induced by the carcinogen. Moreover, ginger extract normalize serum hepatic tumor markers. Histopathological examination of liver tissue also correlated with the biochemical observations. These findings suggest a protective effect of ginger extract against premalignant stages of liver cancer in the DEN-initiated and CCl(4) -promoted hepatocarcinogenesis model in rats.

Protective effects of oral arabic gum administration on gentamicin-induced nephrotoxicity in rats.

Arabic gum (AG) is a complex polysaccharide used as suspending agent. It has been widely used by eastern folk medicine practitioners as a restorative agent and is thought to be an excellent curative for renal failure patients. We therefore tested these folkloric claims using a rat model of gentamicin (GM)-induced nephrotoxicity. AG (7.5g 100ml(-1), in drinking water) was administered orally for 8 days concurrently with GM (80mgkg(-1) per day, i.p.). Estimation of urine volume, serum creatinine and urea concentrations, kidney tissue malondialdehyde (MDA) contents and glutathione (GSH) were carried out after the last dose of GM. Kidneys were also examined for histological changes. GM caused a marked nephrotoxicity as evidenced by significant increases in urine volume (295%), serum creatinine (318%) and urea (258%) and a significant decrease in creatinine clearance (Ccr) (26%). Treatment with AG protected the rats from GM-induced nephrotoxicity as evident by normalisation of these parameters. In addition there was about 187% increase in kidney tissue MDA contents above the control with GM treatment. AG totally prevented the GM-induced rise in kidney tissue contents of MDA. Kidney histology of the tissue from GM-treated rats showed necrosis and desquamation of tubular epithelial cells in renal cortex as well as interstitial nephritis. Whereas it was very much comparable to control when AG was co-administered with GM. In conclusion, AG protected the rats from GM-induced nephrotoxicity, possibly, at least in part through inhibition of the production of oxygen free radicals that cause lipid peroxidation.

Protection effects of Taurine supplementation against cisplatin-induced nephrotoxicity in rats.

BACKGROUND: Taurine, which is the major intracellular free beta-amino acid, is known to be an antioxidant and a membrane-stabilizing agent. This study was designed to investigate the protective role of taurine supplementation against cisplatin-induced nephrotoxicity. METHODS: Male Wistar rats were divided into six groups and treated as follows: (1) saline-treated control drinking tap water, (2) saline-treated plus taurine-supplemented (1.5% taurine in the drinking water), (3) saline-treated plus taurine-depleted (3% beta-alanine in the drinking water), (4) cisplatin-treated, CDDP 6 mg/kg intraperitoneally, (5) taurine-supplemented plus CDDP-treated and (6) taurine-depleted plus CDDP-treated. Rats were sacrificed 7 days after CDDP treatment, and serum as well as kidneys were isolated and analyzed. RESULTS: CDDP-treated rats showed increased kidney weight as a percentage of total body weight, serum creatinine and BUN levels and decreased serum albumin and calcium levels. Also, CDDP treatment resulted in a depletion of kidney GSH content, a reduction in the kidney glutathione peroxidase (GSH-Px) activity and increased kidney MDA production level. Taurine supplementation attenuated CDDP-induced nephrotoxicity which was manifested by jeopardizing the elevation in serum creatinine and BUN levels and the reduction in serum albumin and calcium levels. Moreover, taurine supplementation restored kidney GSH content and GSH-Px activity and reduced platinum accumulation and MDA production levels in the kidney tissue following CDDP treatment. Histopathological examination of the kidney of CDDP-treated rats revealed tubular atrophy, tubular necrosis and desquamation of renal tubular cells. However, taurine supplementation protected against CDDP-induced histopathological changes. CONCLUSIONS: The data suggest that taurine supplementation effectively attenuates the accumulation of platinum within kidney tissue and counteracts the deleterious effect of CDDP on the renal tubular function.