Studies of Hepatic Warm Ischemia in the Obese Zucker Rat

Koneru, Baburao; Reddy, M. Chandra Sekhar; Torre, Andrew de la; Patel, Deepan; Ippolito, Tobi; Ferrante, Robert J.

doi:10.1097/00007890-199504150-00003

Cited by 71 publications

(86 citation statements)

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“…1,12,13,36 However, our measurements of major antioxidants indicate that the antioxidant defense system of obese animals was not compromised compared to hearts from lean animals. In fact, compared to hearts from lean animals, myocardial levels of the thiol antioxidant, glutathione, were increased in both the highfat-fed and fatty (faafa) groups.…”

Section: Compromised Antioxidant Defensementioning

confidence: 75%

“…12,36 Furthermore, diets enriched in fats (either saturated or unsaturated) are also associated with increased lipid peroxidation in several tissues such as aorta, liver and plasma. 23,36 The current study provides novel data that obesity induced by either the leptin receptor defect or high-fat feeding is associated with similar levels of oxidative injury.…”

Section: Overview Of Principal ®Ndingsmentioning

confidence: 99%

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Mechanism for obesity-induced increase in myocardial lipid peroxidation

et al. 2001

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OBJECTIVE:To determine the mechanisms underlying the obesity-induced increase in myocardial lipid peroxidation in the faafa rat. We hypothesized that elevated heart work (ie rate-pressure product), an increased rate of superoxide (O 2 À ) production, total myocardial lipid content, andaor insuf®cient antioxidant defenses are potential contributors to myocardial lipid peroxidation in obesity. DESIGN: Comparative, experimental study of myocardial tissue in 16-week-old lean control (Faa?, normal diet), obese high-fat fed (Faa?, 45% dietary fat), and obese fatty (faafa, normal diet) Zucker rats. MEASUREMENTS: Myocardial work (heart rate Â systolic blood pressure), myocardial lipid content, oxidative and antioxidant enzyme activities (citrate synthase (CS), catalase (CAT), glutathione peroxidase (GPX), superoxide dismutase (SOD)), the rate of papillary muscle superoxide radical production in vitro, thiol content, basal and post-oxidative challenge myocardial lipid peroxidation levels using thiobarbituric reactive acid substances (TBARS) and lipid hydroperoxides (PEROX) as indices of lipid peroxidation. RESULTS: Compared to lean controls, the high-fat fed and fatty animals had similar elevations (P`0.05) in myocardial TBARS and PEROX (23%, 25% and 29% 45%, respectively; P`0.05), and elevated susceptibilities to oxidative stress in vitro following exposure to oxidizing agents (P`0.05). Resting heart work was slightly higher (P`0.05) in both the high-fat fed and fatty animals compared to controls. Myocardial lipid content, SOD activities and non-protein thiol (glutathione) levels were elevated (P`0.05) in high-fat fed and fatty animals compared to controls. The rate of superoxide formation by isolated papillary muscles in vitro did not differ among groups (P`0.05). Regression analysis revealed that the myocardial lipid content contributed most to myocardial lipid peroxidation (R 2 0.76, P`0.05). CONCLUSIONS: Myocardial oxidative injury is closely associated with myocardial lipid content, but is not closely correlated with heart work, insuf®cient antioxidant defenses or a greater rate of superoxide production.

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Section: Compromised Antioxidant Defensementioning

confidence: 75%

Section: Overview Of Principal ®Ndingsmentioning

confidence: 99%

Mechanism for obesity-induced increase in myocardial lipid peroxidation

et al. 2001

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“…The decreased TOC and GSH levels in the nontreated fatty livers are indicative of oxidative stress, a finding consistent with our earlier documentation of increased levels of malondialdehyde-a lipid peroxidation product-in fatty livers. 8 In Ob Zucker rats maintained on defined dietary amounts of TOC, Bieri et al also showed decreased TOC:lipid ratios in the livers. 26 In the same model in a more recent report, a vitamin E-enriched diet led to normalization of markedly elevated levels of 8-epi-prostaglandin F 2␣ , another marker of lipid peroxidation.…”

Section: Discussionmentioning

confidence: 97%

“…1 Lipid peroxidation products in the liver are increased in both models of rat fatty liver. 8,9 Reactive oxygen intermediates are key mediators of I/RP injury in solid organs. Thus, a 2-step oxidative injury comprised of a chronic oxidative stress before and an additional acute oxidative stress following I/RP may explain the increased injury sustained by fatty livers following both cold and warm ischemia.…”

mentioning

confidence: 99%

Oxidative stress in fatty livers of obese Zucker rats: Rapid amelioration and improved tolerance to warm ischemia with tocopherol

2001

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Fatty livers in humans and rats are less tolerant of ischemia, endotoxin, and alcohol. We hypothesized that fatty livers of obese (Ob) Zucker rats are oxidatively stressed and oxidative stress could be relieved by antioxidant treatment, leading to improved tolerance to ischemia. Total glutathione (GSH), tocopherol (TOC), ascorbic acid (AA), catalase (CAT), superoxide dismutase (SOD), and selenium-glutathione peroxidase (Se-GPx) were measured in the livers of Ob and lean (Ln) Zucker rats before and after treatment with high-dose TOC and ascorbate. Also, survival in treated Ob rats following a lethal 90 minutes of partial in vivo warm ischemia was examined. Fatty livers of Ob rats contained significantly less GSH, TOC, and CAT, in comparison with livers of Ln rats. Immunoblotting showed significantly decreased CAT protein without changes in mRNA in fatty livers. There were no significant differences in AA, SOD, and Se-GPx between the 2 groups. Pretreatment with TOC and ascorbate over 48 hours completely corrected the decreases in GSH, TOC, and CAT. Most importantly, TOC with or without ascorbate pretreatment significantly improved survival in Ob rats following ischemia in a dosedependent manner. Fatty livers in humans and experimental animals are more prone to a variety of insults such as ischemia/reperfusion (I/ RP), endotoxin, and alcohol. Nonalcoholic steatohepatitis and its progression to cirrhosis are well-defined clinical entities. 1 Recipients of human donor livers with moderate or severe steatosis have decreased graft and patient survival. 2 Although exact figures are not available, it is believed that as many as 30% of donor livers have varying degrees of steatosis on routine microscopic examination. About 10% of donor livers are not used for transplantation because of moderate to severe steatosis, and this worsens the current shortage of livers. 2 Treatment regimens that will improve tolerance of fatty livers to the aforementioned insults are needed, and would benefit a diverse group of patients.Two rodent models of fatty liver, the genetically obese (Ob) and lipotrope-deficient diet models, are used in the laboratory to further investigate the problems associated with fatty livers. Abnormalities in sinusoidal microcirculation, 3,4 mitochondrial oxidative phosphorylation including a decrease in adenosine triphosphate production, 5,6 and dysregulation of cytokine production 7 are some of the mechanisms that have been associated with the increased injury to fatty livers in both rodents and humans. Oxidative stress has recently been postulated to be a common feature in fatty livers of diverse etiologies. 1 Lipid peroxidation products in the liver are increased in both models of rat fatty liver. 8,9 Reactive oxygen intermediates are key mediators of I/RP injury in solid organs. Thus, a 2-step oxidative injury comprised of a chronic oxidative stress before and an additional acute oxidative stress following I/RP may explain the increased injury sustained by fatty livers following both cold and warm ischemia.To...

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“…Other reports support this ®nding that obese Zucker rats have an increased fat accumulation in many tissues and organs, and this increase in fat is associated with elevated lipid peroxidation. 25 A possible mechanism to explain this observation is that an increased PUFA in tissues promotes lipid oxidation by increasing the amount of substrate available for peroxidation. Human studies investigating the oxidation of serum lipoproteins have shown similar results.…”

Section: Obesity and Myocardial Fat Contentmentioning

confidence: 99%

Obesity is associated with increased myocardial oxidative stress

et al. 1999

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OBJECTIVE: To determine: 1) whether obesity predisposes the myocardium to oxidative stress as evidenced by higher tissue levels of myocardial lipid peroxidation, and 2) what cellular mechanisms are responsible for this predisposition. DESIGN: Comparative, descriptive study of the myocardial tissue of lean and obese Fatty Zucker animals. ANIMALS: 12 month old lean ( 7 afa; n 6; mean body weight 590 g) and obese (faafa; na 7; mean body weight 882 g) male Fatty Zucker rats. MEASUREMENTS: Basal lipid peroxidation (assessed using thiobarbituric reactive acid substances (TBARS) and cumene hydroperoxide equivalents), oxidative and antioxidant enzyme activities (citrate synthase (CS), superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT), thiol content, heat shock protein expression (HSP72a73) and TBARS concentrations following an iron-mediated challenge in vitro. RESULTS: Compared to lean, lipid peroxidation was greater (P`0.05) in the left ventricle (LV) from obese rats as indicated by higher levels of lipid hydroperoxides (mean 11.48 vs 13.7 cumene hydroperoxide equivalents (CHPE)amg lipid) and TBARS (mean 11.1 vs 13.9 nMolamg lipid.). The activity of the manganese isoform of superoxide dismutase in the LV was higher (P`0.05) in obese animals, compared to controls (mean 135 vs 117 Uamg protein). In contrast, LV catalase and glutathione peroxidase activities did not differ (P b 0.05) between groups. Also, LV levels of HSP 72 (inducible) and 73 (constitutive) did not differ (P b 0.05)( between lean and obese animals. Following an iron-stimulated oxidative challenge in vitro, TBARS concentration was signi®cantly greater (P`0.05) in LV of obese rats compared to the lean (mean 12.7 vs 16.7 nMolamg lipid). CONCLUSIONS: These results support the notion that obesity predisposes the myocardium to oxidative stress. However, the postulate that obesity is associated with elevated myocardial antioxidant enzyme activities and HSPs was only partially supported by these ®ndings.

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Studies of Hepatic Warm Ischemia in the Obese Zucker Rat

Cited by 71 publications

References 0 publications

Mechanism for obesity-induced increase in myocardial lipid peroxidation

Mechanism for obesity-induced increase in myocardial lipid peroxidation

Oxidative stress in fatty livers of obese Zucker rats: Rapid amelioration and improved tolerance to warm ischemia with tocopherol

Obesity is associated with increased myocardial oxidative stress

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