Topical trans-resveratrol ameliorates steroid-induced anterior and posterior segment changes in rats.

Steroid-induced hypertension and glaucoma is associated with increased extracellular meshwork (ECM) deposition in trabecular meshwork (TM). Previous studies have shown that single drop application of trans-resveratrol lowers IOP in steroid-induced ocular hypertensive (SIOH) rats. This IOP lowering is attributed to activation of adenosine A1 receptors, which may lead to increased matrix metalloproteinase (MMP)-2 activity. This study evaluated the effect of repeated topical application of trans-resveratrol for 21 days in SIOH animals on IOP, changes in MMP-2 level in aqueous humor, trabecular meshwork and retinal morphology and retinal redox status. We observed that treatment with trans-resveratrol results in significant and sustained IOP reduction in SIOH rats. This IOP reduction is associated with significantly higher aqueous humor total MMP-2 level; significantly reduced TM thickness and increased number of TM cells. Treatment with trans-resveratrol also significantly increased ganglion cell layer (GCL) thickness, the linear cell density in the GCL and inner retina thickness; and significantly reduced retinal oxidative stress compared to the SIOH vehicle-treated group. In conclusion, repeated dose topical application of trans-resveratrol produces sustained IOP lowering effect, which is associated with increased level of aqueous humor MMP-2, normalization of TM and retinal morphology and restoration of retinal redox status.

Effects of an indigenous contraceptive herbal formulation on gonadotrophs of the pituitary gland of the rat.

An indigenous contraceptive herbal formulation consisting of a mixture of Lepidagathis longifolia, Palaquium sp and Phyllagathis rotundifolia is being used by the Temuan Aborigins of Malaysia. Although the previous studies demonstrated that this contraceptive herbal formulation causes anovulatory estrous cycle, altered circulating hormone levels and fetal resorption in rats, but the effects of this formulation on the gonadotrphs of the pituitary gland are yet to be evaluated. The present study was designed to observe the morphometric changes of the gonadotrophs and the plasma concentrations of follicle stimulating hormone and leutinizing hormone. Thirty five Sprague-Dawley adult female rats were randomly divided into 5 groups. Experimental animals were given a combined herbal extract or individual herbal extract at a dose of 540 mg/kg/day subcutaneously for 7 days. Immunostained gonadotrophs were studied by using image analyzer. FSH and LH serum concentrations were determined using RIA. The FSH and LH concentrations were low in animals that received combined herbal extract (p<0.01). FSH concentration was noted to be significantly low in animals that received P. rotundifolia (p<0.05). The mean cell area and cell density of gonadotrophs of animals that received combined herbal extract were significantly low compared to control group (p<0.05). It was concluded that the herbal extracts do suppress the production of gonaotrophins along with the demonstrable suppresive effect on the FSH cells.

Anterior and posterior segment changes in rat eyes with chronic steroid administration and their responsiveness to antiglaucoma drugs.

Steroid-induced ocular hypertension (SIOH) is associated with topical and systemic use of steroids. However, SIOH-associated anterior and posterior segment morphological changes in rats have not been described widely. Here we describe the pattern of intraocular pressure (IOP) changes, quantitative assessment of trabecular meshwork (TM) and retinal morphological changes and changes in retinal redox status in response to chronic dexamethasone treatment in rats. We also evaluated the responsiveness of steroid-pretreated rat eyes to 5 different classes of antiglaucoma drugs that act by different mechanisms. Up to 80% of dexamethasone treated animals achieved significant and sustained IOP elevation. TM thickness was significantly increased and number of TM cells was significantly reduced in SIOH rats compared to the vehicle-treated rats. Quantitative assessment of retinal morphology showed significantly reduced thickness of ganglion cell layer (GCL) and inner retina (IR) in SIOH rats compared to vehicle-treated rats. Estimation of retinal antioxidants including catalase, superoxide dismutase and glutathione showed significantly increased retinal oxidative stress in SIOH animals. Furthermore, steroid-treated eyes showed significant IOP lowering in response to treatment with 5 different drug classes. This indicated the ability of SIOH eyes to respond to drugs acting by different mechanisms. In conclusion, SIOH was associated with significant morphological changes in TM and retina and retinal redox status. Additionally, SIOH eyes also showed IOP lowering in response to drugs that act by different mechanisms of action. Hence, SIOH rats appear to be an inexpensive and noninvasive model for studying the experimental antiglaucoma drugs for IOP lowering and neuroprotective effects.