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Updated: May 22, 2026

Developing a Clinically Relevant Hemorrhagic Shock Model in Rats
Published on: March 22, 2024
Protective effect of crocetin on hemorrhagic shock-induced acute renal failure in rats
Yunbo Wang1, Junling Yan, Liang Xi
1Faculty of Training Administration, Department of Medical Education, The Fourth Military Medical University, Xi'an, People's Republic of China.
Abstract:
Multiple organ failure is a common outcome of hemorrhagic shock followed by resuscitation, and the kidney is one of the prime target organs involved. The main objective of the study was to evaluate whether crocetin, a natural product from Gardenia jasminoides Ellis, has beneficial effects on renal dysfunction caused by hemorrhagic shock and resuscitation in rats. Anesthetized rats were bled to reduce mean arterial blood pressure to 35 (SD, 5) mmHg for 60 min and then were resuscitated with their withdrawn shed blood and normal saline. Crocetin was administered via the duodenum at a dose of 50 mg/kg 40 min after hemorrhage. The increase in creatinine and blood urea nitrogen was significantly reduced at 2 h after hemorrhage and resuscitation in crocetin-treated rats. The increases in renal nitric oxide, tumor necrosis factor α, and interleukin 6 were also attenuated by crocetin. Hemorrhagic shock resulted in a significant elevation in malondialdehyde production and was accompanied by a reduction in total superoxide dismutase activity, activation of nuclear factor κB, and overexpression of inducible nitric oxide synthase. These changes were significantly attenuated by crocetin at 2 h after resuscitation. These results suggested that crocetin blocks inflammatory cascades by inhibiting production of reactive oxygen species and restoring superoxide dismutase activity to ameliorate renal dysfunction caused by hemorrhage shock and resuscitation.
Insights
Crocetin, a natural compound, significantly protects kidneys from damage caused by hemorrhagic shock and resuscitation in rats. It reduces inflammation and oxidative stress, improving kidney function.
Area of Science:
- Nephrology
- Pharmacology
- Toxicology
Background:
- Hemorrhagic shock and resuscitation commonly lead to multiple organ failure, with the kidney being a primary target.
- Renal dysfunction following hemorrhagic shock poses a significant clinical challenge.
Purpose of the Study:
- To investigate the protective effects of crocetin, a natural product from Gardenia jasminoides Ellis, against renal dysfunction induced by hemorrhagic shock and resuscitation in a rat model.
- To elucidate the underlying mechanisms of crocetin's renoprotective action.
Main Methods:
- Rats were subjected to hemorrhagic shock (mean arterial blood pressure of 35 mmHg for 60 min) followed by resuscitation.
- Crocetin (50 mg/kg) was administered orally 40 minutes after hemorrhage.
- Renal function markers (creatinine, blood urea nitrogen), inflammatory cytokines (TNF-α, IL-6), oxidative stress markers (MDA, SOD activity), and key signaling molecules (NF-κB, iNOS) were assessed.
Main Results:
- Crocetin treatment significantly reduced elevated creatinine and blood urea nitrogen levels 2 hours post-resuscitation.
- Crocetin attenuated increases in renal nitric oxide, tumor necrosis factor-α, and interleukin-6.
- Crocetin administration inhibited malondialdehyde production, restored total superoxide dismutase activity, and reduced nuclear factor-κB activation and inducible nitric oxide synthase overexpression.
Conclusions:
- Crocetin demonstrates significant renoprotective effects against hemorrhagic shock and resuscitation-induced injury in rats.
- The protective mechanism involves blocking inflammatory cascades, inhibiting reactive oxygen species production, and restoring antioxidant capacity.
- Crocetin represents a potential therapeutic agent for mitigating kidney damage in conditions of hemorrhagic shock.

