Antioxidant effect of acetyl-l-carnitine against cisplatin-induced cardiotoxicity.

OBJECTIVE: Cisplatin (CDDP) toxicity is a dose-limiting clinical problem in clinical practice, mainly because of nephrotoxicity or ototoxicity. However, the mechanism of CDDP-induced cardiotoxicity is poorly understood. Acetyl-l-carnitine (ALCAR) is an antioxidant agent with protective effects against the side effects of various chemotherapeutics. CDDP-induced cardiotoxicity and the protective role of ALCAR were evaluated in this study. METHODS: Morphological changes were evaluated in hematoxylin and eosin-stained sections, and immunohistochemistry for caspase-3, superoxide dismutase-2 (SOD-2), inducible nitrite oxide synthase (iNOS), cyclooxygenase-2, and Bcl-2 was performed using the hearts of athymic nude mice carrying xenograft neuroblastoma tumors. Mice were randomized (six/group) to the control, CDDP (16 mg/kg), and ALCAR (200 mg/kg)+CDDP (16 mg/kg) groups. Results were analyzed using nonparametric tests. RESULTS: No difference was observed in the rates of cardiac necrosis, dilated/congested blood vessels, hemorrhage, polymorphonuclear leukocyte infiltration, edema, and pyknotic nuclei among the groups. SOD-2 expression was increased in the CDDP group but not in the ALCAR+CDDP group. iNOS, Bcl-2, and caspase-3 levels were not significantly different among the groups. CONCLUSIONS: ALCAR might be a candidate protective agent for CDDP-induced cardiotoxicity. SOD-2, as a member of the oxidant system, should be evaluated in further studies as a biomarker of cardiotoxicity.

Effect of 1- and 6-Hour-Delayed Corneal Collagen Cross-Linking on Corneal Healing in a Rabbit Alkali-Burn Model: Clinical and Histological Observations.

PURPOSE: To study the effect of 1- and 6-hour-delayed corneal collagen cross-linking (CXL) on wound-healing of experimental alkali burns of the cornea. METHODS: Twenty-four albino rabbits were used. Alkali burns were created using 1 M NaOH. The animals were divided randomly into 2 groups: group 1 (control group, n = 6) and group 2 (experimental group, n = 18). The experimental group was further divided into 3 subgroups as follows: group 2A, untreated (non-CXL) subgroup; group 2B, 1-hour-delayed CXL treatment subgroup; and group 2C, 6-hour-delayed CXL treatment subgroup. All rabbits were examined periodically for 21 days after treatment and then killed. The corneas were excised and histologically examined. RESULTS: Corneal ulceration, edema, and opacity scores were 4.0 ± 1.64, 1.6 ± 0.65, and 3.5 ± 1.21 in group 2A, 1.5 ± 1.76, 1.3 ± 0.87, and 3.1 ± 1.12 in group 2B, and 2.0 ± 1.90, 1.5 ± 0.79, and 3.3 ± 1.09 in group 2C, respectively. These scores were significantly less in groups 2B and 2C than in group 2A (P = 0.023, P = 0.043, and P = 0.034, respectively). Corneal epithelialization, evident upon staining, was best in group 2B and worst in group 2A (P = 0.012). Histopathology revealed that destruction of corneal collagen fibers and infiltration of inflammatory cells into corneal tissue were reduced in groups 2B and 2C compared with group 2A. CONCLUSIONS: We found that CXL treatment exerted positive effects on severe alkali-induced corneal burns. However, the effects were more pronounced in the 1-hour treatment group. We believe that CXL treatment may be a possible treatment for corneal alkali burn.