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Journal of Parenteral and Enteral Nutrition
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Original Communications

Sesame Oil Does Not Show Accumulatively Enhanced Protection Against Oxidative Stress–Associated Hepatic Injury in Septic Rats

Dur-Zong Hsu, DVM, PhD1, Se-Ping Chien, MS2, Ya-Hui Li, MS1 and Ming-Yie Liu, PhD1,3

From the 1 Department of Environmental and Occupational Health, National Cheng Kung University Medical College, Tainan, Taiwan; 2 Department of Living Science, Tainan Woman's College of Arts and Technology, Tainan, Taiwan; and3 Sustainable Environment Research Centre, National Cheng Kung University, Tainan, Taiwan.

Address correspondence to: Ming-Yie Liu, PhD, Department of Environmental and Occupational Health, National Cheng Kung University Medical College, 138 Sheng-Li Road, Tainan 70428, Taiwan; e-mail: myliu{at}mail.ncku.edu.tw.

Background: Sepsis is one of the major causes of death reported in intensive care units. A daily supplement of sesame oil for 1 week significantly attenuates oxidative stress–associated hepatic injury in septic rats. However, the excess intake of sesame oil may be associated with a health risk. This study investigates the effect of accumulative sesame oil on oxidative stress–associated hepatic injury after cecal ligation and puncture in rats. Methods: Sesame oil was administered daily (4 mL/kg/d, orally) to rats, and the total intake of sesame oil ranged from 0 (control) to 140 mL/kg before cecal ligation and puncture in 9 groups of rats. Oxidative stress was examined by determining the levels of lipid peroxidation and glutathione. Hepatic injury was evaluated by measuring serum levels of aspartate aminotransferase and alkaline phosphatase. Results: Rats that received sesame oil for 4 and 5 weeks had a lower body weight gain compared with those that received saline. Lipid peroxidation was decreased in the 20-mL/kg and 28-mL/kg groups, but it was increased in the 140-mL/kg group compared with the control group. Glutathione levels were increased in the ≤28-mL/kg groups compared with the control group. Serum levels of aspartate aminotransferase and alkaline phosphatase were reduced in the ≤28-mL/kg groups compared with the control group. Conclusion: Sesame oil does not demonstrate accumulatively enhanced protection against oxidative stress–associated hepatic injury after cecal ligation and puncture in rats.

Key Words: sesame oil • oxidative stress • hepatic damage • sepsis • rats

Sepsis, a systemic inflammatory response syndrome, is one of the major causes of death reported in intensive care units.1-3 In the United States, for example, more than 200,000 patients die of sepsis every year.4 Despite advances in critical care medicine, the mortality rate has not decreased significantly during the past 2 decades.5 Oxidative stress is known to be involved in the development of hepatic failure and death in sepsis; however, the effect of antioxidants used in managing sepsis is limited.6,7

Sesame oil, derived from the plant species Sesamum indicum L., consists of fatty acid and nonfat antioxidants, such as sesamin,8 tocopherol,9 sesamolin,10 and sesaminol,10 which may contribute to the antioxidative effect of sesame oil.9 Sesame oil has been regarded as a daily nutritional supplement to increase cell resistance to lipid peroxidation.11 Tripeptide glutathione (L-{gamma}-glutamyl-L-cysteinyl-glycine), the major thiol in mammalian cells, is increased in sesame oil–treated rats with endotoxin-induced oxidative stress.12 Furthermore, sesame oil given immediately or after endotoxin administration attenuates oxidative stress–associated hepatic disorder.13

We reported that daily supplement of sesame oil (4 mL/kg/d) for 1 week significantly attenuates oxidative stress–associated hepatic injury, which is not affected by corn oil or mineral oil in cecal ligation and puncture (CLP)–induced sepsis in rats.14 However, it is demonstrated that excess intake of various plant oils may be associated with a health risk by reducing body weight gain.15 Thus, the aim of this study was to examine the effect of accumulated sesame oil on oxidative stress–associated hepatic injury after CLP in rats.


   Methods
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Methods
Results
 Discussion
 
Materials
Sesame oil was obtained from Sigma (St Louis, MO).

Animals
Male SPF Wistar rats weighing 200 -250 g were obtained and housed in our institution's laboratory animal center. Rats were housed individually in a room with a 12-hour light-dark cycle and central air conditioning (25°C, 70% humidity). They were allowed free access to tap water and pelleted rodent diet (Richmond Standard; PMI Feeds, Inc, St Louis, MO). The animal care and experimental protocols were in accord with nationally approved guidelines.

Experimental Design
Experiment 1. Twelve rats were divided into 2 groups (n = 6). These rats were gavaged with saline (4 mL/kg/d; saline group) or sesame oil (4 mL/kg/d; sesame oil group), and the total intake of saline or sesame oil was 0, 4, 12, 20, 28, 56, 84, 112, and 140 mL/kg, respectively. Body weight gain was measured at 0, 1, 2, 3, 4, and 5 weeks after sesame oil administration.

Experiment 2. Ninety rats were divided into 2 groups. These rats were gavaged with saline (4 mL/kg/d; saline group) or sesame oil (4 mL/kg/d; sesame oil group), and the total intake of saline or sesame oil was 0, 4, 12, 20, 28, 56, 84, 112, and 140 mL/kg, respectively. CLP was conducted for 12 hours after sesame oil administration.14 Oxidative stress was examined by determining lipid peroxidation and glutathione levels. Hepatic function was evaluated by determining serum levels of aspartate aminotransferase (AST) and alkaline phosphatase (ALKP).

CLP
Rats were anesthetized with light diethylether and then shaved over the anterior abdominal wall. A 2-cm-long midline incision, sufficient to expose the cecum and the adjacent intestine, was made. The ligated cecum was punctured twice with an 18-gauge needle, after which the cecum was gently squeezed to exude fecal matter. The abdominal incision was then closed, and 1 mL of saline was administered subcutaneously for fluid resuscitation.14,16

Blood Collection
Rat blood samples were collected from the femoral vein under light diethylether anesthesia. Blood was drawn by venipuncture into serum-separation tubes, allowed to clot for 30 minutes at room temperature, and then centrifuged at 1000g for 10 minutes at 4°C.

Measuring Serum Lipid Peroxidation Level
Blood samples were collected in tubes containing ethylenediaminetetraacetic acid as an anticoagulant. Whole blood (500 µL) was centrifuged at 2500g for 10 minutes at 4°C. Supernatant (200 µL) was taken for lipid peroxidation measurement by a commercial assay kit (Lipid Peroxidase Assay Kit; Calbiochem-Novabiochem Co, Darmstadt, Germany), and the spectrophotometer was read at 586 nm.17

Measuring Glutathione Level
Blood samples were collected in tubes containing the anticoagulant heparin. Five hundred microliters of whole blood was centrifuged at 2500g for 10 minutes at 4°C. The plasma supernatant was discarded, and the red blood cell pellet was washed 3 times in ice-cold 0.9% NaCl. The erythrocyte pellet was resuspended in 4 volumes of 6% metaphosphoric acid at 4°C, mixed thoroughly, and centrifuged at 3000g for 10 minutes at 4°C. One hundred microliters of supernatant was used to assess the glutathione level with an assay kit (Glutathione Assay Kit; Calbiochem-Novabiochem), and the spectrophotometer was read at 400 nm.

Evaluating Hepatic Injury
Hepatic dysfunction was assessed by determining the levels of AST and ALKP. Serum samples were spotted to slides (Vitros DT; Johnson & Johnson Inc, Rochester, NY) and evaluated for both indicators by a blood biochemical analyzer (Ektachem DTSCII; Eastman Kodak, Rochester, NY).

Statistical Analysis
Data are expressed as the mean ± standard deviation. Significant differences between measurements traits were analyzed using the independent Student t-test method. Statistical significance was set at P < .05.


   Results
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Methods
 Results
Discussion
 
Effects of Sesame Oil on Body Weight Gain After CLP
Rats that received sesame oil (4 mL/kg/d) for 4 and 5 weeks decreased body weight gain compared with the saline group (Figure 1).


Figure 1
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  		Figure 1. Effects of sesame oil on body weight gain. Rats were given saline (4 mL/kg/d, orally) or sesame oil (4 mL/kg/d, orally) for 1, 2, 3, 4, and 5 weeks, respectively. Body weight was measured at 0, 1, 2, 3, 4, and 5 weeks, respectively. Body weight gain was determined using the 0-week group as the basal line. Data are expressed as the mean ± SD (n = 6). Significant differences in measurement traits were analyzed using the Student t test. *P < .05 compared with the saline group.

 


Figure 2
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  		Figure 2. Effects of sesame oil on lipid peroxidation in cecal ligation and puncture (CLP)–treated rats. Rats were given saline (4 mL/kg/d, orally; saline group) or sesame oil (4 mL/kg/d, orally; sesame oil group). The total intake of sesame oil ranged from 0 to 140 mL/kg. Serum lipid peroxidation was determined 12 hours after CLP. Data are expressed as the mean ± SD (n = 5). *P < .05 compared with the saline group.

 


Figure 3
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  		Figure 3. Effects of sesame oil on serum glutathione in cecal ligation and puncture (CLP)–treated rats. Rats were given saline (4 mL/kg/d, orally; saline group) or sesame oil (4 mL/kg/d, orally; sesame oil group). The total intake of sesame oil ranged from 0 to 140 mL/kg. The serum glutathione level was determined 12 hours after CLP. Data are expressed as the mean ± SD (n = 5). *P < .05 compared with the saline group.

 
Effects of Sesame Oil on Serum Lipid Peroxidation After CLP
To examine the effect of sesame oil on oxidative stress in CLP-treated rats, lipid peroxidation was determined. Compared with the saline group, CLP-induced lipid peroxidation was reduced in the 20-mL/kg and 28-mL/kg groups. In contrast, CLP-induced lipid peroxidation was enhanced in the 140-mL/kg group compared with the saline group (Figure 2).

Effects of Sesame Oil on Serum Glutathione After CLP
We further examined the glutathione levels involved in the effect of sesame oil on oxidative stress in CLP-treated rats. Glutathione levels were increased in the 12-, 20-, and 28-mL/kg groups compared with the saline group (Figure 3). No difference was found in the rest of the groups.

Effects of Sesame Oil on Hepatic Injury After CLP
To examine the effect of sesame oil on hepatic injury induced by CLP, serum levels of AST and ALKP were determined. In CLP-treated rats, serum levels of AST were reduced in both the 20-mL/kg and 28-mL/kg groups compared with the saline group. On the other hand, the levels of ALKP were reduced in the 4-, 12-, 20-, and 28-mL/kg groups compared with the saline group (Figure 4).


Figure 4
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  		Figure 4. Effects of sesame oil on serum aspartate aminotransferase (AST) and alkaline phosphatase (ALKP) levels in cecal ligation and puncture (CLP)–treated rats. Rats were given saline (4 mL/kg/d, orally; saline group) or sesame oil (4 mL/kg/d, orally; sesame oil group). The total intake of sesame oil ranged from 0 to 140 mL/kg. AST and ALKP were assessed 12 hours after CLP. Data are expressed as the mean ± SD (n = 5). *P < .05 compared with the saline group.

 


   Discussion
Top
Methods
 Results
 Discussion
 
Although a 1-week daily supplement of sesame oil showed potent attenuation of oxidative stress and hepatic injury,14 rats that ingested sesame oil every day for a longer period of time or in the presence of hyperlipidemia caused by the administration of large amounts of sesame oil did not show accumulatively enhanced protection against oxidative stress–associated hepatic injury after CLP. A previous study8 indicated that a sesame oil–rich diet (5 wt%) significantly increases the survival rate in CLP-treated mice. However, we found that sesame oil (4 mL/kg/d) given to rats for more than 1 week did not further protect against oxidative stress–associated hepatic injury after CLP. Nevertheless, whether chronic intake of smaller amounts of sesame oil presents a health hazard is unknown. Further investigation will be needed.

Excess intake of sesame oil reduced body weight gain in rats. This is consistent with the finding that excess intake of various plant oils, such as coconut oil, olive oil, palm oil, and sunflower oil, reduces body weight gain compared with normal diets in mice.15 Excess intake of sesame oil no longer attenuated its protection against hepatic injury induced by oxidative stress in CLP-treated rats, although sesame oil attenuates hepatic injury and increases the survival rate by reducing oxidative stress.8,18

Accumulation of polyunsaturated fatty acids (PUFAs) in the bloodstream caused by overingesting sesame oil may lead to the neutralization of the antioxidative effects of sesame oil. The primary fatty acids in sesame oil are monounsaturated oleic acid (18:1 {omega}-9; 39.9%) and polyunsaturated linoleic acid (18:2 {omega}-6; 42.3%).19 Sesame oil contains a high level of PUFAs, which are important targets of free radical attack.8 When rats are exposed to CLP-induced oxidative stress, PUFAs may be attacked by free radicals and oxidized into lipid peroxides.20,21 Furthermore, experimental data support the notion that accumulation of n-6 PUFAs may increase lipid peroxidation.22,23 A daily intake of n-6 or n-3 PUFAs that is greater than 10% of total energy is not recommended because a high dietary intake of PUFAs implies health risks.19 The dietary requirement of antioxidants from a diet rich in PUFAs has not been defined.21 It is important to note that daily sesame oil supplement protects against endotoxemia or sepsis, which may be attributed to the antioxidant components in sesame oil.8,12 Nonfat sesame oil lignan sesamol may contribute to the antioxidation of sesame oil in septic rats.24,25 It is plausible that adverse effects of sesame oil on lipid peroxidation is associated with PUFAs in sesame oil. More investigation is needed to confirm this.

Glutathione has been shown to eliminate the harmful oxidant26 and to prevent tissue damage caused by excessive oxidative stress.27,28 In the present study, glutathione was significantly decreased after excess sesame oil administration. Our observation was in accordance with a study indicating that glutathione is decreased during severe oxidative stress in endotoxemic animals.29 We suggest that the defect of the sesame oil–exerted protection results from the increase of lipid peroxidation and/or the decrease of glutathione production during sepsis.

In summary, daily supplement of sesame oil (4 mL/kg/d) for more than 1 week may not have accumulatively enhanced protection against oxidative stress–associated hepatic injury after CLP in rats.

We thank Drs Y. C. Chang and Y. C. Chuang for valuable discussion. We also thank Bill Franke for editorial assistance.


  
Top
Methods
 Results
 Discussion
 
Financial disclosure: This research was supported by grants 96AS-14.2.1-BQ-B6 from the Taiwan Bureau of Animal and Plant Health Inspection and Quarantine; NSC-96-2628-B-006-038-MY3 from the National Science Council, Taiwan; and DOH92-TD-1009 from the Taiwan Department of Health.

Received for publication October 8, 2007. Accepted for publication December 20, 2007.

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Journal of Parenteral and Enteral Nutrition, Vol. 32, No. 3, 276-280 (2008)
DOI: 10.1177/0148607108316193
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