br Conflict of interest br Acknowledgements

Conflict of interest

Acknowledgements
The authors would like to acknowledge Universiti Malaysia Pahang, for its support through PGRS research Grant No. GRS 130336. PK also appreciates IPS for the financial assistance in the form of DSS.

Introduction
Venomous and poisonous snakes are a significant cause of global morbidity and mortality. They are found almost throughout the world, including many oceans and have evolved a variety of highly effective cgrp antagonist and methods of delivery. Their impact on humans is considerable, most current data suggest that they cause in excess of 3 million bites per year with more than 150,000 deaths, particularly in rural tropical areas (White, 2000).
The pyramid viper (Echis pyramidum) is one of the venomous snakes found in Saudi Arabia. It is widely spread in Jazan which according to surveillance, extends from A-Darb city north to Al-Mousam city in the south, near the Saudi-Yemeni borders and from Jazan city west to Fifa and Al-Da’r cities in the east. The pyramid viper has been related with the majority of envenomation cases in the region. The victims of bites who were examined in the local hospitals were suffering from symptoms of nausea and vomiting, swelling at bitten place, low blood pressure, painful bitten site, sweating, bleeding in the area of bite, nose bleeding, fever and unconsciousness (Al-Shammari et al., 2013). Efforts have been made to correlate the toxicity of snake venoms to their enzymatic activities. Owing to the diverse character of the venom and the antagonistic behavior of its different components, it is advantageous to utilize purified venom fractions in place of crude venom for diverse toxicological and pharmacological studies.
Clinical symptoms of E. pyramidum envenomation are characterized by highly complex pathophysiological features of local as well as systemic nature. Crude venom of viper Echis genus caused renal dysfunction in envenomated Guinea pigs (Warrell, 1993; Salman, 2009). In addition, Al-Asmari et al. (2014) concluded that the acute phase oxidative stress due to Echis pyramidum venom (EPV) injection points toward the importance of an early antioxidant therapy for the management of snake bites. From this point, the aim of our study was to investigate the effect of different doses of EPV at different times on the renal tissue of rats.

Materials and methods

Results

Discussion
Relatively little work has been done on the toxicological effects of crude EPV. Okuda et al. (2001) purified novel disintegrins, the platelet aggregation inhibitors pyramidin A and B from the venom of E. pyramidum. Al-Asmari et al. (2006) studied the effect of crude venom on time-course of lipid peroxidation in different organs of mice. El-Missiry et al. (2010) investigated the effect of crude venom on the activities of certain serum enzyme of mice. Wahby et al. (2012) isolated purified hemorrhagic metalloproteinase enzyme from EPV and studied its hemorrhagic activities in the skin of rabbit. Most recently, Conlon et al. (2013) isolated [Ser49] phospholipase A2 from the venom of the saw-scaled vipers Echis ocellatus, Echis pyramidum leakeyi, Echis carinatus sochureki, and Echis coloratus and observed their cytotoxic activity against human non-small cell lung adenocarcinoma A549 cells. So, this work was undertaken to study the effect of EPV on histological, molecular changes and on oxidative stress status in renal homogenates.
Snake venom components, especially those of viper venoms, activate, inhibit or liberate enzymes by destroying cellular organelles (Abdel-Nabi et al., 1997; Marsh et al., 1997). The different toxic effects of viper venoms are due to their proteolytic and lipolytic enzymes (Tan and Ponnudurai, 1990). Common initial signs of envenomation are hypoglycemia (Abu-Sinna et al., 1993), general metabolic disturbance (Mahmoud, 1983), muscular dystrophy (Mohamed and Khaled, 1966), nephrotoxicity (Ickowicz et al., 1966) and cytotoxicity (Bertke and Atkins, 1961).