Calcium dobesilate protects against d-galactose-induced hepatic and renal dysfunction, oxidative stress, and pathological damage.

Calcium dobesilate (CaD) is used for the treatment of diabetic retinopathy and nephropathy. This agent exerts antioxidant effects. In the present study, we evaluated the protective effects of oral administration of CaD against hepatorenal damages in a mice model of aging induced by d-galactose (d-gal). We used 28 male albino mice, which equally and randomly were divided into four groups as follows: intact, aging (d-gal at the dose of 500 mg/kg, p.o.), aging + CaD 50 (d-gal plus CaD at the dose of 50 mg/kg), and aging + CaD 100 (d-gal plus CaD at the dose of 100 mg/kg, p.o.). All drugs were administered orally once a day for 42 days. The liver and kidney damages were evaluated by measuring mass indices, levels of serum creatinine and blood urea nitrogen, and activities of serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase and by histopathological evaluation. Moreover, hepatic and renal tissue oxidant/antioxidant markers (malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase) were measured. The results showed that d-gal treatment induced significant oxidative stress in the kidney and liver that was paralleled by dysfunctions and histological alterations of these organs. CaD significantly improved the liver and kidney indices, implemented functional capacity of the liver and kidney, as well as decreased oxidative stress enhancing antioxidative enzyme activities. CaD treatment also inhibited the development of histological alterations of both kidney and liver. CaD might represent a promising therapeutic agent for the attenuation of hepatorenal injuries induced by aging.

Calcium Dobesilate and Micro-vascular diseases.

Micro-vascular diseases and its associated complications continue to be a significant health problem worldwide. Vascular lesions from microvascular involvement lead to impaired blood flow and contribute to damage and dysfunction of one or more target organs, that is, the heart, kidneys, eyes, and nervous system. Calcium Dobesilate Drug (CAD) is an established vasoactive and angioprotective drug that has shown a unique, multitarget mode of action in several experimental studies and in different animal models of diabetic microvascular complications. CAD has been widely used as an antioxidant and a vascular protective agent. At present, the application of Calcium Dobesilate is mainly related to Micro-vascular damage-related diseases, such as diabetic retinopathy (DR) and diabetic nephropathy (DN), and it is found to significantly improve the related symptoms. Its beneficial effects make it an attractive therapeutic compound especially in the early stages of these diseases. Scholars at home and abroad have studied the effectiveness, safety, and mechanisms of the related diseases, furthermore, the subjects involved patients and animal models, they have found some new clinical effects of this medicine. This paper makes a brief summary of a research progress of clinical application about Vascular injury related diseases and other aspects.

Pharmacokinetics of calcium dobesilate in beagle dogs after a single administration.

A pharmacokinetic study was carried out in beagle dogs after a single intravenous infusion of 100 mg/kg of calcium dobesilate, a dose claimed to produce a cardiac lymphagogue effect. This effect on cardiac lymphatics is known to contribute to the reduction of myocardial infarct size after coronary artery occlusion. At the end of the intravenous infusion, which lasted about 30 minutes, the plasma level was 263 +/- 68 micrograms/ml, falling to 56 +/- 23 micrograms/ml by the third hour. This high plasma level of calcium dobesilate between the end of the infusion and the 3rd hour might explain the pharmacological effect of the drug on the cardiac lymphatic system.

Pharmacokinetics of calcium dobesilate in beagle dogs after repeated administration.

Many pharmacological findings suggest that repeated intravenous administration of calcium dobesilate improves myocardial lymphatic drainage, accelerates removal of degradation products and other toxic substances by increasing the number of functioning lymphatics and thus limits infarct size after experimental coronary artery occlusion. The aim of the present study was to investigate the relationship between the blood levels of calcium dobesilate and the pharmacological effect described above using the same dosage schedule. During the first six hours after intravenous administrations, at one hour interval, of three doses each of 100 mg/kg of calcium dobesilate, the average plasma level ranged from 414 micrograms/ml to 95 micrograms/ml with a plateau between the second and fourth hour. During this period, which is the most crucial for the ischemic myocardium, the effect of calcium dobesilate attained its optimum as evidenced by a statistically significant increase in the number of lymphatics visualized by lymphangiography and the reduction of infarct size measured by planimetry, by weight or by tomography. The plasma levels before the 18th hour were still higher than 10 micrograms/ml but no measurable calcium dobesilate was detected in the plasma at the 20th hour which indicates total elimination of the drug from the blood and thus precluding any risk of accumulation. The present results confirm that the doses of calcium dobesilate used in the pharmacological studies correspond to an adequate blood level.

Bioavailability studies of calcium dobesilate--a case of flip-flop kinetics.

Absolute and relative bioavailability of two commercial calcium dobesilate tablets were evaluated in ten healthy volunteers in a cross-over trial using a newly developed HPLC detection method. Both tablet forms were absorbed completely but very slowly thus leading to a flip-flop kinetics. It could be shown that AUC values derived from flip-flop models were comparable with those of normal i. v. kinetics.