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Histological, molecular and biochemical detection of renal injury after Echis pyramidum snake envenomation in rats
Awadh M Al-Johany1, Mohamed K Al-Sadoon1, Ahmed E Abdel Moneim2
1Department of Zoology, College of Science, King Saud University, Saudi Arabia.
Abstract:
Nephrotoxicity is a common sign of snake envenomation. The present work aimed to clarify the effect of intraperitoneal injection of 1/8 LD50 and 1/4 LD50 doses of Echis pyramidum snake venom on the renal tissue of rats after 2, 4 and 6 h from envenomation. Histopathological examination showed intense dose and time dependent abnormalities, including swelling glomerulus and tubular necrosis and damage as well as signs of intertubular medullary hemorrhage at early stages of envenomation. However, at late stages of envenomation by any of the doses under investigation, no intact renal corpuscles were recorded and complete lysis in renal corpuscles with ruptured Bowman's capsules was observed. Immunohistochemistry by immunohistochemical staining was used to test the protein expression of Bax in renal tissue of rats. The result showed that the expression of Bax in renal tissue sections of envenomated rats was increased according to dose and time-dependant manner. The isolation of DNA from the renal cells of envenomed rats pointed out to the occurrence of DNA fragmentation, which is another indicator for renal tissue injury especially after 6 h of 1/4 LD50 of E. pyramidum envenomation. Oxidative stress biomarkers malondialdehyde and nitrite/nitrate levels, antioxidant parameters; glutathione, total antioxidant capacity and catalase were assayed in renal tissue homogenates. The venom induced significant increase in the levels of malondialdehyde and nitrite/nitrate while the levels of glutathione, total antioxidant capacity and catalase were significantly decreased, especially after 6 h of envenomation. The results revealed that the E. pyramidum induced dose and time-dependant significant disturbances in the physiological parameters in the kidney. We conclude that the use of the immunohistochemical techniques, the detection of DNA integrity and oxidative stress marker estimations are more specific tools that can clarify cellular injury and could point out to the defense activity of the renal tissue at envenomation.
Insights
Echis pyramidum snake venom causes significant kidney damage in rats, leading to cellular injury and DNA fragmentation. This study highlights specific biomarkers for assessing nephrotoxicity and renal defense mechanisms.
Area of Science:
- Toxicology
- Pathology
- Biochemistry
Background:
- Nephrotoxicity is a frequent complication of snake envenomation.
- Echis pyramidum envenomation poses a significant health risk, particularly concerning kidney damage.
Purpose of the Study:
- To investigate the dose- and time-dependent effects of Echis pyramidum venom on rat renal tissue.
- To evaluate specific biomarkers indicative of kidney injury and cellular defense mechanisms following envenomation.
Main Methods:
- Histopathological examination of renal tissues at 2, 4, and 6 hours post-envenomation.
- Immunohistochemical staining for Bax protein expression.
- DNA fragmentation analysis.
- Assay of oxidative stress (malondialdehyde, nitrite/nitrate) and antioxidant (glutathione, total antioxidant capacity, catalase) biomarkers.
Main Results:
- Histopathology revealed dose- and time-dependent renal abnormalities, including glomerular swelling, tubular necrosis, and hemorrhage, progressing to complete lysis of renal corpuscles.
- Bax protein expression and DNA fragmentation increased significantly with venom dose and time.
- Elevated malondialdehyde and nitrite/nitrate levels, coupled with decreased glutathione, total antioxidant capacity, and catalase, indicated significant oxidative stress.
Conclusions:
- Echis pyramidum venom induces severe, dose- and time-dependent nephrotoxicity in rats.
- Immunohistochemistry, DNA integrity assessment, and oxidative stress markers are valuable tools for evaluating venom-induced renal injury and the kidney's defense responses.
