Comparison of the Prophylactic Effect of Silymarin and Deferoxamine on Iron Overload-Induced Hepatotoxicity in Rat

Najafzadeh, Hossein; Jalali, Mehrdad; Morovvati, Hassan; Taravati, Farnaz

doi:10.1007/s13181-010-0030-9

Cited by 33 publications

(22 citation statements)

References 36 publications

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“…Iron chelator, DEF, is often used to treat genetic or acquired iron accumulation. By the essential characteristic of binding iron, DEF is also widely used to protect oxidative stress and reduce the damage to various organs and tissues, such as the liver . NAC is an antioxidant that provides protective effect to resist injury caused by ROS, being proven via regulation of the JNK/Bcl‐2 pathway …”

Section: Discussionmentioning

confidence: 99%

“…By the essential characteristic of binding iron, DEF is also widely used to protect oxidative stress and reduce the damage to various organs and tissues, such as the liver. 23 NAC is an antioxidant that provides protective effect to resist injury caused by ROS, being proven via regulation of the JNK/Bcl-2 pathway. 24 In our study, we observed viability of hepatocyte spheroids stored in HTK and the addition of DEF and/or NAC.…”

Section: Albumin Production and Gene Expressionmentioning

confidence: 99%

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Cold storage of porcine hepatocyte spheroids for spheroid bioartificial liver

Chen

Shaheen

et al. 2019

Xenotransplantation

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Background and aims Cell‐based therapies for liver disease such as bioartificial liver rely on a large quantity and high quality of hepatocytes. Cold storage was previously shown to be a better way to preserve the viability and functionality of hepatocytes during transportation rather than freezing, but this was only proved at a lower density of rat hepatocytes spheroids. The purpose of this study was to optimize conditions for cold storage of high density of primary porcine hepatocyte spheroids. Methods Porcine hepatocytes were isolated by a three‐step perfusion method; hepatocyte spheroids were formed by a 24 hours rocked culture technique. Hepatocyte cell density was 5 × 106/mL in 1000 mL spheroid forming medium. Spheroids were then maintained in rocked culture at 37°C (control condition) or cold stored at 4°C for 24, 48 or 72 hours in four different cold storage solutions: histidine‐tryptophan‐ketoglutarate (HTK) alone; HTK + 1 mM deferoxamine (DEF); HTK + 5 mM N‐acetyl‐L‐cysteine (NAC); and HTK + 1 mM DEF + 5 mM NAC. The viability, ammonia clearance, albumin production, gene expression, and functional activity of cytochrome P450 enzymes were measured after recovery from the cold storage. Results In this study, we observed that cold‐induced injury was reduced by the addition of the iron chelator. Viability of HTK + DEF group hepatocyte spheroids was increased compared with other cold storage groups (P < 0.05). Performance metrics of porcine hepatocyte spheroids cold stored for 24 hours were similar to those in control conditions. The hepatocyte spheroids in control conditions started to lose their ability to clear ammonia while production of albumin was still active at 48 and 72 hours (P < 0.05). In contrast, the viability and functionality of hepatocyte spheroids including ammonia clearance and albumin secretion were preserved in HTK + DEF group at both 48‐ and 72‐hour time points (P < 0.05). Conclusions The beneficial effects of HTK supplemented with DEF were more obvious after cold storage of high density of porcine hepatocyte spheroids for 72 hours. The porcine hepatocyte spheroids were above the cutoff criteria for use in a spheroid‐based bioartificial liver.

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Section: Discussionmentioning

confidence: 99%

Section: Albumin Production and Gene Expressionmentioning

confidence: 99%

Cold storage of porcine hepatocyte spheroids for spheroid bioartificial liver

Chen

Shaheen

et al. 2019

Xenotransplantation

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“…Previous studies confirmed that the iron-chelating properties of a plant directly related to its flavonoids content (39). Najafzadeh et al demonstrated that silymarin as a flavonoid could decrease iron overloadinduced liver toxicity and its effects were similar to deferoxamine (40). In another study showed that baicalin (a commercial flavonoid) has iron chelating and liver protective effects in iron overload mice (36).…”

mentioning

confidence: 82%

The Protective Effects of Hydro-Alcoholic Extract of Coriandrum sativum in Rats with Experimental Iron-Overload Condition

Talaei

Kheirollah

Babaahmadi‐Rezaei

et al. 2017

Jundishapur J Nat Pharm Prod

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Background: Development of a new iron-chelating medication may eventually serve as treatment of iron overload diseases, such as thalassemia and other iron related disorders. Coriander sativum, a plant rich of phenol and flavonoids, has an iron-chelating effect in-vitro. The ethanolic extract of C. sativum was investigated for its in-vivo ameliorating effect on hepatic damage in rats with experimental iron overload. Methods: Twenty-four adult male wistar rats were randomly divided to 4 groups: healthy control, iron overload, iron overload treated with deferoxamine, and 200 mg/kg of C. sativum extract, respectively. Assessments were performed for serum iron, ferritin, and serum markers of hepatic and cardiac damages, antioxidant enzyme, and lipid peroxidation levels. Results:The results indicated serum iron and ferritin concentration were significantly increased in the iron overload group compared to healthy controls (P < 0.05). Treatment with C. sativum extract significantly decreased iron and ferritin concentration (P < 0.05). Histopathological changes in the liver, kidney, and the cardiac system, and iron accumulation in the liver were observed in the iron overload group compared to healthy controls (P < 0.05). Treatment with C. sativum extract significantly decreased biochemical parameters, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and Creatinine phosphokinase (CPK), and improved tissue damage and decreased iron accumulation in the liver compared to the iron overload group (P < 0.05). Conclusions:The study showed that the hydro-alcoholic extract of C. sativum has iron-chelating and liver protective effects similar to deferoxamine against experimental iron overload condition in rats.

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“…27 The second condition included HTK and deferoxamine (DEF), which is known to reduce oxidative stress and tissue damage. 28 The third condition included HTK and N-acetyl-L-cysteine (NAC), a known protective antioxidant. 29 The final condition combined the three supplements, HTK, DEF, and NAC.…”

Section: Hepati C and Pan Cre Ati C Xenotr Ans Pl Antation Update Smentioning

confidence: 99%