Protective Effect of Crocetin on Hemorrhagic Shock–Induced Acute Renal Failure in Rats

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were bled to reduce mean arterial blood pressure to 35 (SD, 5) mmHg for 60 min and then were resuscitated with their withdrawn shed blood and normal saline.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.

Crocetin induces apoptosis of BGC-823 human gastric cancer cells

“…This inhibition was associated with reduced cell proliferation through the downregulation or upregulation of certain apoptotic proteins, including cytochrome c and cleaved caspase-3 expression. In addition, a number of pharmacological studies have demonstrated crocetin to have multiple activities, including anti-inflammatory (35,36) and anti-oxidant (37,38) effects. Therefore, it was hypothesized that the anti-oxidant and anti-inflammatory effects of crocetin may also be considered to be involved in several synergistic antitumor mechanisms (39,40).…”

Molecular mechanisms of trauma-induced acute kidney injury: Inflammatory and metabolic insights from animal models

“…Moreover, despite consistent methods, the creatinine levels were not always increased to the same degree by the injury [73], highlighting the substantial challenge of variability in animal models of AKI that inherently comes with in vivo studies. A similar study performed by Wang et al demonstrated that the increased MDA levels after HS in rats was reduced by treatment with the antioxidant crocetin [58]. These researchers concluded that although HS reduced total SOD, crocetin provided protection by elevating total SOD.…”

“…iNOS and NO production are also generated during hypoxia in rat proximal tubules [58,61] . NO derived from iNOS propagates the inflammatory response and contributes to enhanced tissue damage.…”

“…ROS and NOS facilitate the translocation of the transcription factor nuclear factor κ-B (NF-κB) from the cytoplasm to the nucleus, which elicits the inflammatory cascade. Once in the nucleus, NF-κB initiates expression of iNOS [49,51], tumor necrosis factor α (TNF-α) [58][59][60] and interleukin 6 (IL-6); all elevated in rat kidneys within 2 hours of hemorrhagic shock and…”

Forensic Medical Aspects of Complications and Lesions of Target Organs with Hemorrhagic Shock

“…Пошкодження клітин нирки викликає ішемію тканин, яка ініціює складний і взаємопов'я-заний ланцюг подій, а оксид азоту відіграє вирі-шальну роль в нирковій функції і може інгібуватись аміногуанідіном (AГ) [3,7,16].…”