Comparative Evaluation of Neuroprotective Activity of Tryptanthrin and Its Oxime in Middle Cerebral Artery Occlusion in Rats.

The neuroprotective activity of tryptanthrin and its oxime was compared in male Wistar rats with a model of intraluminal occlusion of the middle cerebral artery. Neurobehavioral tests were performed 4, 24, and 48 h after focal cerebral infarction (FCI) using a modified neurological severity score (mNSS); additionally, the horizontal stability test, the plantar sensitivity test of the fore and hind limbs, holding on the tilted cage top test, and negative geotaxis test were performed. The size of FCI and the severity of brain tissue swelling were examined on day 2 after occlusion. Tryptanthrin and its oxime were administered at a dose of 10 mg/kg intraperitoneally during FCI, then daily for 2 days. In the control group, the mean score of neurological deficit remained at a high level for 2 days. FCI size was 43.8±3.4% of hemisphere area, and the hemisphere volume increased by 18.5±2.0% due to brain tissue swelling and edema. Administration of tryptanthrin and its oxime significantly decreased neurological deficits at all control points and reduced FCI size (by 24.2 and 30.4%, respectively) and brain tissue swelling of the affected hemisphere (by 64.9 and 62.7%, respectively). Therefore, the neuroprotective effect of tryptanthrine and its oxime in the acute period of FCI is largely determined by their anti-inflammatory activity.

Bioavailability of the Phenolic Antioxidant 4-Methyl-2,6-Diisobornylphenol After Oral Administration.

We compared bioavailability of 4-methyl-2,6-diisobornylphenol after single intragastric administration to rats in a dose of 200 mg/kg in starch suspension and in almond oil. Absorption of 4-methyl-2,6-diisobornylphenol in the gastrointestinal tract after administration in almond oil was much more efficient than after administration in aqueous starch mucus.

Hemorheological effects of ortho-isobornyl phenol derivative under conditions of brain ischemia in rats.

Hemorheological activity of 4-methyl-2,6-di-isobornyl phenol, a new o-isobornyl phenol derivative, was studied under conditions of experimental prolonged partial cerebral ischemia. Brain ischemia is associated with hemorheological disorders which can be characterized as blood hyperviscosity syndrome: increased viscosity of the whole blood (within a wide range of shear rates), plasma viscosity, fibrinogen content in blood plasma, and platelet aggregation; deterioration of platelet deformability and reduced availability of oxygen for tissues. A course (5 days) of intragastric 4-methyl-2,6-di-isobornyl phenol (100 mg/kg) prevented the development of blood hyperviscosity syndrome by modulating blood macrorheology (reduction of plasma viscosity and fibrinogen content) and microrheology (reduction of erythrocyte aggregation and improvement of their deformability).

Morphological changes in retinal neurons in streptozotocin-induced diabetes mellitus and their correction with an isobornylphenol derivative.

Along with microangiopathy, one of the main causes of blindness in diabetic retinopathy consists of degeneration of retinal neurons. Electron microscopy and morphometric analysis were used to study structural changes in neurosensory cells, associative, and ganglion neurons in the retina in 30 while mongrel male rats with streptozotocin diabetes for two months and the effects of a new semisynthetic antioxidant 4-methyl-2,6-diisobornylphenol, a screened phenol, were evaluated. Destructive changes were found to affect the outer segments of neurosensory cells and ganglion neurons. The number density of neurosensory and ganglion cells decreased, and the proportion of these cells with pyknotic nuclei increased. 4-Methyl-2,6-diisobornylphenol had neuroprotective actions, preventing destructive changes to neurosensory cells and ganglion neurons.

Antithrombogenic and antiplatelet activity of optho-isobornyl phenol derivative.

We studied antithrombogenic and antiplatelet properties of 4-methyl-2,6-diisobornyl phenol, a new promising compound belonging to ortho-isobornyl phenol derivatives, under conditions of intravascular thrombosis and acute cerebral ischemia. It was found that 4-methyl-2,6-diisobornyl phenol prevents intravascular thrombus formation by reducing platelet aggregation and improving antiplatelet activity of the vascular wall.