الفهرس 
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Abstract
The skin is the largest multifunctional organ in the body. It absorbs ultraviolet radiation, combats microorganism invasion and chemical penetration, and regulates the passage of water and electrolytes. The skin also plays a major role in thermoregulation, in addition to performing immunological, sensory, and autonomic functions.
Isotretinoin, which is also known as 2-cis-vitamin A or 13-cis-retinoic acid is a naturally occurring metabolite of vitamin A. It is an orally active drug for the treatment of severe refractory acne that functions by reducing sebaceous gland size and sebum production. However, like all oral retinoids, isotretinoin has a spectrum of toxicity.
Tiron, 4, 5-dihydroxy-1, 3-benzenedisulfonic, is an alpha-tocopherol analog. It acts as a superoxide scavenger and nontoxic iron chelator. It is a mitochondrial localized antioxidant that can permeabilize the organelle membrane and accumulate inside. Tiron is also a vitamin E analog and acts as a direct hydroxyl radical (OH ). It is widely used antioxidant to rescue reactive oxygen species (ROS) evoked cell death.
This work was designed to focus on the histological and immunohistochemical changes induced by isotretinoin on the skin of adult male albino rats and the possible protective role of tiron.
Materials and Methods:
Sixty adult male albino rats, each weighing 100-150gm were used in this study and were randomly divided into four groups:
group I (control group)
It was composed of 10 rats were given the vehicle (DMSO and saline) IP daily for 4 weeks.
group II (Tiron treated group)
It was composed of 10 rats treated with tiron orally for 4 weeks.
group III (Isotretinoin treated group)
It was composed of 20 rats treated with isotretinoin for 4 weeks. The animals were subdivided into two equal subgroups:
IIIa: Rats were treated with isotretinoin at a dose of 6mg/kg/day by intraperitoneal injection daily for 4 weeks.
IIIb: Rats were treated with isotretinoin at a dose of 3mg/kg/day by intraperitoneal injection daily for 4 weeks.
group IV: (Combined isotretinoin and tiron treated group)
It was composed of 20 rats treated with isotretinoin and tiron for 4 weeks.The animals were subdivided into two equal subgroups:
IVa: Rats were treated with tiron together with isotretinoin at a dose of 6mg/kg/day for 4 weeks.
IVb: Rats were treated with tiron together with isotretinoin at a dose of 3mg/kg/day for 4 weeks.
At the end of each determined period, the animals from all groups were anesthetized using ether inhalation then were sacrificed, and the skin of each animal was shaved and excised. Then they were fixed in 10% formol saline& processed for paraffin blocks then 5-6 micrometer sections were cut and stained with H&E, Mallory trichrome stain and PAS for routine histological and histochemical examination and with Cytokeratin 5/6, Ki 67 and Epithelial membrane antigen (EMA) antibody for Immunohistochemical study. Morphometric study and statistical analysis were done.