Crocin has anti-inflammatory and protective effects in ischemia-reperfusion induced renal injuries

Objective(s): Crocus sativus (saffron) has been widely used in traditional medicine. It has also been found to possess many beneficial properties in modern medicine. The most important ingredients of saffron are crocin, crocetin, safranal, and picrocrocin. This study evaluated the protective effects of crocin against the inflammation, oxidative stress, and functional disturbances of the kidney induced by renal ischemia/reperfusion (I/R). Materials and Methods: Different doses of crocin (0, 100, 200, and 400 mg/kg) were administered intraperitoneally 30 min before I/R. The rats of the sham group were also injected with normal saline before the sham surgery. For induction of I/R, both renal artery and vein clamped for 30 min, bilaterally. The I/R-induced renal injuries were assessed by measuring leukocyte infiltration, intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-alpha (TNF-α) mRNA expression levels, malondialdehyde (MDA) and ferric reducing/antioxidant power (FRAP) levels in the kidney tissue, and plasma creatinine and urea-nitrogen concentrations. Results: Except for the tissue level of FRAP which decreased, all other measured parameters increased following I/R induction. Pretreatment with all doses of crocin significantly reduced the severity of these disturbances (P

Therapeutic potential of active components of saffron in post-surgical adhesion band formation

Background Abdominal adhesions are common and often develop after abdominal surgery. There are currently no useful targeted pharmacotherapies for adhesive disease. Saffron and its active constituents, Crocin and Crocetin, are wildly used in traditional medicine for alleviating the severity of inflammatory or malignant disease. Purpose The aim of this study was to investigate the therapeutic potential of the pharmacological active component of saffron in attenuating the formation of post-operative adhesion bands using different administration methods in a murine model. Material method saffron extract (100 mg/kg), Crocin (100 mg/kg), and Crocetin (100 mg/kg) were administered intraperitoneally and by gavage in various groups of male Wistar rat post-surgery. Also three groups were first treated intra-peritoneally by saffron extract, Crocin, and Crocetin (100 mg/kg) for 10 days and then had surgery. At the end of the experiments, animals sacrificed for biological assessment. Result A hydro-alcoholic extract of saffron and crocin but not crocetin potently reduced the adhesion band frequency in treatment and pre-treatment groups in the mice given intra-peritoneal (i.p) injections. Following the saffron or crocin administration, histological evaluation and quantitative analysis represented less inflammatory cell infiltration and less collagen composition, compared to control group. Moreover, the oxidative stress was significantly reduced in treatment groups. Conclusion These findings suggest that a hydro-alcoholic extract of saffron or its active compound, crocin, is a potentially novel therapeutic strategy for the prevention of adhesions formation and might be used as beneficial anti-inflammatory or anti-fibrosis agents in clinical trials. Taxonomy Abdominal surgeries/post-surgical adhesions

Protective Effect of P-Coumaric Acid against Cisplatin-Induced Nephrotoxicity and Hepatotoxicity in Rats

Background and purpose: Cisplatin is used in chemotherapy for cancer patients. But, it has adverse effects on some organs, including the kidney and liver. P-coumaric acid is a polyphenolic substance with multiple biological properties. The present study aimed to investigate the effect of p-coumaric acid on renal and hepatic side effects of cisplatin. Materials and methods: This experimental study was performed in 21 male rats that were randomly divided into three groups. In the sham group, 20% ethanol was gavaged for 7 days. The experimental group I received 20% ethanol for 7 days + a single dose of cisplatin )8 mg/kg( at day 5. The experimental group II received cisplatin (8 mg/kg at day 5) + p-coumaric acid (100 mg/kg/day) for 7 days. The functional disturbances of kidney and liver were assessed by measuring the blood levels of creatinine, urea-nitrogen, AST, ALT, and ALP. Also, measuring MDA and FRAP levels in kidney and liver tissues were used to assess oxidative stress. The tissue damages were also assessed by studying H&E stained slides. Results: Cisplatin administration increased the concentrations of creatinine, urea-nitrogen, AST, ALT, ALP, MDA, tissue damages, and decreased FRAP. Application of p-coumaric acid led to complete or relative improvements in functional parameters of kidney and liver, and reduced tissue damages and MDA level. The FRAP level was found to increase by the p-coumaric acid. Conclusion: P-coumaric acid demonstrated a protective effect against the side effects of cisplatin in the kidneys and liver

Protective effect of crocin on gentamicin-induced nephrotoxicity in rats

Objective(s): Gentamicin is used for the treatment of Gram-negative bacterial infections. However, gentamicin administration is limited because of nephrotoxicity. The aim of the present study was to evaluate the protective effect of crocin against gentamicin-induced nephrotoxicity in rats. Materials and Methods: Thirty two male Wistar rats received gentamicin (100 mg/kg, IP), with or without crocin (100 mg/kg, IP) for seven consecutive days. Plasma creatinine and urea-nitrogen concentrations, oxidative stress and histopathological changes of kidney tissues were monitored. Results: Administration of gentamicin resulted in significant increases in plasma creatinine and urea-nitrogen concentrations and renal tissue malondialdehyde (MDA) level, and a decrease in the renal tissue ferric reducing/antioxidant power (FRAP) level. Crocin decreased plasma creatinine and urea-nitrogen concentrations and tissue MDA level, but increased the level of tissue FRAP. In addition, gentamicin led to cellular damages including glomerular atrophy, cellular desquamation, tubular necrosis and fibrosis, epithelial oedema of proximal tubules, perivascular edema, vascular congestion and intra-tubular proteinaceous casts, all of which were partially recovered by crocin. Conclusion: Crocin has protective effects against functional disturbances, oxidative stress and tissue damages induced by gentamicin

Therapeutic effects of curcumin on the functional disturbances and oxidative stress induced by renal ischemia/reperfusion in rats

Objectives: Curcumin has anti-inflammatory and antioxidative properties. The objective of this study was to investigate the therapeutic effects of curcumin on functional disturbances, oxidative stress, and leukocyte infiltration induced by renal ischemia/reperfusion (I/R). Materials and Methods: Animals were randomly divided into 9 groups. The groups with 24-h reperfusion consisted of sham-24h, I/R-24h, and three I/R groups treated with curcumin at 10, 20, or 30 mg kg-1, i.p. after the ischemic period. The 72-h reperfusion groups also included Sham-72h, I/R-72h, I/R treated with curcumin at single dose of 20 mg kg-1, i.p., and I/R group which received three doses of curcumin at 20 mg kg-1, i.p., consecutively. Renal functional injury was assessed by measuring serum creatinine and urea-nitrogen concentrations. Oxidative stress was evaluated by assessment tissue malondialdehyde (MDA) and the ferric reducing/antioxidant power (FRAP) levels. Moreover, renal tissue leukocyte infiltration was measured by histopathology examination. Results: Ischemia/reperfusion resulted in a significant increase in serum concentration of creatinine, urea-nitrogen, tissue MDA level, and leukocytes infiltration as well as reduced FRAP level. Treatment with curcumin in 24-h reperfusion groups could only lead to a significant change in the levels of MDA and FRAP. However, in 72-h reperfusion groups, curcumin was able to correct all functional disturbances, oxidative stress, and leukocytes infiltration with more effectiveness in groups that received three doses of curcumin. Conclusion: The administration of curcumin during 72-h reperfusion following 30 minutes of ischemia can decrease renal oxidative stress and leukocytes infiltration as well as improve kidney function. However, during first 24-h reperfusion, curcumin only decreased oxidative stress

Protective effect of Malva sylvestris L. extract in ischemia-reperfusion induced acute kidney and remote liver injury.

Mallow (Malva sylvestris L.) has had medicinal and therapeutic uses in addition to its oral consumption. The present study was conducted to examine the protective effect of Malva sylvestris L. extract on ischemia-reperfusion-induced kidney injury and remote organ injuries in the liver. Before ischemia-reperfusion, rats in the different groups received intraperitoneal normal saline or mallow extract at the doses of 200, 400 or 600 mg/kg of body weight. After 30-minutes of bilateral renal ischemia followed by 24-hours of reperfusion, tissue damage in the kidney and liver samples were determined through studying H&E-stained slides under a light microscope. The degree of leukocyte infiltration and tissue mRNA expressions of TNF- and ICAM-1 were then measured to examine the degree of renal inflammation. The renal tissue MDA and FRAP levels were measured for determining the amount of oxidative stress. Plasma concentrations of creatinine, urea, ALT and ALP were also measured. Ischemia-reperfusion led to a significant increase in plasma concentrations of creatinine, urea, ALT and ALP, and renal tissue MDA, and a significant decrease in renal tissue FRAP. The expression of pro-inflammatory factors in the kidney tissue, the level of leukocyte infiltration and the amount of tissue damage in the kidney and liver also increased. Pretreatment by mallow extract led to a significant improvement in all the variables measured. The 200- and 400-mg doses yielded better results in most parameters compared to the 600-mg dose. The findings showed that mallow extract protects the kidney against ischemia-reperfusion and reduces remote organ injury in the liver

Representing histopathologic alterations in kidneys of rats that underwent sham (A), ischemia/reperfusion and pretreated with normal saline (B), or malva silvestris extract at 200, 400, or 600 mg/kg (C-E).

<p>(Haematoxylin-Eosin, 400x).</p

Light microscopic images of renal cortex for representing leukocyte infiltration in rats that underwent sham surgery (A), those that underwent renal ischemia/reperfusion while pretreated with saline (B) or 200, 400, or 600 mg/kg malva silvestris extract (C-E); and leukocyte infiltration as mean ± SE per square millimeters (F).

<p>Magnification: 400X.</p

Protective effect of <i>Malva sylvestris L</i>. extract in ischemia-reperfusion induced acute kidney and remote liver injury - Fig 3

<p>Representative semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) of mRNA encoding tumor necrosis factor-alpha (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) (A) in the renal cortex of the sham group (lane 2) and rats that underwent ischemia/reperfusion after pretreatment with normal saline (lane 3) or malva silvestris extract at 200, 400, or 600 mg/kg (lanes 4–6, respectively). Lane 1 is a 100-bp RNA size marker. Densitometric quantification of relative band intensities from RT-PCR assays for TNF-α and ICAM-1 (B).</p> <p>**P < 0.01; ***P < 0.001 in comparison with their own sham group.</p> <p>‡P < 0.05; ‡‡‡P < 0.001 in comparison with their own I/R group.</p