Histological effect of high versus low dose isotretinoin and possible protective role of Tiron on skin of adult male albino rat

Abstract

Background: Isotretinoin is one of the most effective drugs in acne treatment. It is retinoic acid derivative. Systemic administration of isotretinoin may induce many adverse effects. Tiron has antioxidant properties and could ameliorate skin damage and cell apoptosis. Aim of the work: To evaluate the adverse effect of high versus low dose isotretinoin on the skin of adult albino rats and the probable protective effect of tiron. Material and Method: Sixty adult male albino rats were divided into five groups: control group I (DMSO and saline), tiron treated group II (300 mg/kg orally), isotretinoin treated group III (6 mg/kg /day IP), isotretinoin treated group IV (3 mg/kg / day IP), and protective group V which treated with isotretinoin and tiron. Rats of the last group were subdivided into 2 equal subgroups (V a & V b) which received isotretinoin at a dose of 6mg and 3mg /kg/day respectively with tiron. At the end of the studied period, rats were then sacrificed and the samples were taken for histological, histochemical, immunohistochemical and morphometric studies. Results: Animals treated with isotretinoin at a dose of 6mg/kg/day showed thinning of all layers of epidermis. Epidermal cells were degenerated, exfoliated with marked reduction in cellular proliferation and associated with ill-defined basement membrane. Sebaceous glands showed a marked reduction in surface area and some cells appeared degenerated and dermis revealed loss of its normal architecture and increased densely packed collagen fibers seen by Mallory trichrome stain. These degenerative changes were less apparent in administration of isotretinoin at a lower dose of 3mg/kg/day. Concomitant administration of tiron and isotretinoin induced an observable improvement protection against these changes compared to control, especially in low dose. Conclusion: The pronounced skin damage induced by isotretinoin can be ameliorated by joined therapy of tiron and isotretinoin.

Morphological, histopathological, and immunohistochemical changes in tissues of adult male Sprague-Dawley rats orally treated with isotretinoin

“…Inspection of the histopathology of reproductive organs in repeated-dose toxicity investigations in rodents and nonrodents is one of the best assessment approaches executed before the first administration of a novel medication to humans. 2 The articles on the consequences of retinoids on spermatogenesis are opposing. The data from the present research confirmed that testicular tissues from animals treated with ISO at 20 mg/kg/day for seven days exhibited degenerative changes.…”

“…21 It results in a loss of desmosomes and diminishes tonofilaments and glycocalyx cohesion of the cell. 2 Disruption of the Sertoli-germ cell junctions may cause failure of spermatogenesis. The blood-testis barrier is a system of tight junctions between adjacent Sertoli cells to form a vital microenvironment capable of supporting developing germ cells and helping preserve homeostasis.…”

“…1 Most harmful effects regarding the use of ISO are associated with the skin. 2 Since ISO is filtered from the bloodstream by the liver, taking it may exert an extra strain on this organ. Opposing data from human studies were encountered in the literature; some suggested hepatotoxicity, 3 while others claimed no changes in the parenchymal liver in patients who took it at 10-40 mg daily for at least six months.…”