Wan Gyoon Shin

Effects of Astaxanthin on Oxidative Stress in Overweight and Obese Adults

Oxidative stress is caused by an imbalance between the antioxidant and the reactive oxygen species, which results in damage to cells or tissues. Recent studies have reported that oxidative stress is involved in obesity, in addition to many other human diseases and aging. A prospective, randomized, double‐blind study was performed to investigate the effect of astaxanthin (ASX), which is known to be a potent antioxidant, on oxidative stress in overweight and obese adults in Korea. Twenty‐three adults with BMI > 25.0 kg/m2 enrolled in this study and were randomly assigned to two dose groups: ASX 5 mg and 20 mg once daily for 3 weeks. Malondialdehyde (MDA), isoprostane (ISP), superoxide dismutase (SOD) and total antioxidant capacity (TAC), as oxidative stress biomarkers, were measured at baseline and 1, 2 and 3 weeks after ASX administration. Compared with baseline, the MDA (by 34.6% and 35.2%) and ISP (by 64.9% and 64.7%) levels were significantly lowered, whereas SOD (by 193% and 194%) and TAC (by 121% and 125%) levels were significantly increased in two dose groups after the 3 week intervention. This study revealed that supplemental ASX for 3 weeks improved oxidative stress biomarkers by suppressing lipid peroxidation and stimulating the activity of the antioxidant defense system. Copyright

Pharmacokinetics and first-pass metabolism of astaxanthin in rats

Astaxanthin is a carotenoid with antioxidant, anti-cancer and anti-inflammatory properties. The pharmacokinetics of astaxanthin after its intravenous (5, 10, and 20 mg/kg) and oral (100 and 200 mg/kg) administration and its first-pass extraction ratios after its intravenous, intraportal or intragastric (20 mg/kg) administration were evaluated in rats. The pharmacokinetic parameters of astaxanthin were dose dependent after its intravenous administration, due to the saturable hepatic metabolism of astaxanthin, but dose independent after oral administration. The gastrointestinal absorption of astaxanthin followed the flip-flop model. The hepatic and gastrointestinal first-pass extraction ratios of astaxanthin were approximately 0·490 and 0·901, respectively. Astaxanthin was metabolised primarily by hepatic cytochrome P-450 1A1/2 in rats. Astaxanthin was unstable up to 4 h incubation in four rat gastric juices and up to 24 h incubation in various buffer solutions having a pH of 1-13. The tissue/plasma ratios of astaxanthin at 8 and 24 h after its oral administration (100 mg/kg) were greater than unity for all tissues studied, except in the heart, at 8 h, indicating that the rat tissues studied had high affinity for astaxanthin.

Protective Effects of Haematococcus Astaxanthin on Oxidative Stress in Healthy Smokers

Free radicals induced by cigarette smoking have been strongly linked to increased oxidative stress in vivo, contributing to the pathobiology of various diseases. This study was performed to investigate the effects of Haematococcus astaxanthin (ASX), which has been known to be a potent antioxidant, on oxidative stress in smokers. Thirty-nine heavy smokers (≥20 cigarettes/day) and 39 non-smokers were enrolled in this study. Smokers were randomly divided into three dosage groups to receive ASX at doses of 5, 20, or 40 mg (n=13, each) once daily for 3 weeks. Oxidative stress biomarkers such as malondialdehyde, isoprostane, superoxide dismutase, and total antioxidant capacity, and ASX levels in plasma were measured at baseline and after 1, 2, and 3 weeks of treatment. Compared with baseline, the plasma malondialdehyde and isoprostane levels decreased, whereas superoxide dismutase level and total antioxidant capacity increased in all ASX intervention groups over the 3-week period. In particular, isoprostane levels showed a significant dose-dependent decrease after ASX intake. The results suggest that ASX supplementation might prevent oxidative damage in smokers by suppressing lipid peroxidation and stimulating the activity of the antioxidant system in smokers.

Relation of ghrelin, leptin and inflammatory markers to nutritional status in active pulmonary tuberculosis

BACKGROUNDS & AIMS Malnutrition is a prominent feature of tuberculosis. Little is known about the role of the appetite-related hormones, ghrelin and leptin, in malnutrition in tuberculosis. This study was undertaken to determine whether ghrelin and leptin contribute to malnutrition in active pulmonary tuberculosis. METHODS Nutritional parameters and plasma levels of ghrelin, leptin, and inflammatory cytokines were measured before treatment and after clinical improvement following anti-tuberculosis chemotherapy in 23 tuberculosis subjects and 23 healthy controls prospectively. Patients were divided into well-nourished (n=15) and malnourished (n=8) groups. RESULTS Ghrelin but not leptin levels were significantly lower in the malnourished tuberculosis group than in the well-nourished tuberculosis group [44.0 (43.0-54.0) vs. 122 (108-158)pg/mL; p<0.05]. Malnutrition score was negatively correlated to ghrelin (rho=-0.76, p<0.01) but not to leptin levels. TNF-alpha and IL-6 levels were significantly higher in the malnourished tuberculosis group than in the well-nourished tuberculosis group and controls. Plasma levels of ghrelin tended to decrease as inflammatory cytokines increased before treatment. CONCLUSIONS Decreased plasma ghrelin levels, in addition to increased plasma inflammatory cytokine levels, may be associated with malnutrition in active pulmonary tuberculosis.

Safety and efficacy of statin treatment alone and in combination with fibrates in patients with dyslipidemia: a meta-analysis

Abstract Background: Dyslipidemia is a major risk factor for cardiovascular disease and is treated with many effective lipid-lowering agents. Statins are often used alone or in combination with fibrates. Combination therapy is more effective due to their comparative actions, but the increased incidence of side effects should be considered carefully. Research design and methods: A meta-analysis of published data was conducted to compare the safety and efficacy of statins alone versus statins plus fibrates in patients with dyslipidemia. In total, nine articles were assessed for efficacy analysis and ten articles were assessed for safety analysis. Results: In the efficacy analysis, a combination of statins and fibrates provided significantly greater reductions in total cholesterol (SE = 0.430; 95% CI 0.315–0.545), LDL cholesterol (SE = 0.438; 95% CI 0.321–0.555) and triglycerides (SE = 0.747; 95% CI 0.618–0.876), and a significantly greater increase in HDL cholesterol (SE = 0.594; 95% CI 0.473–0.715) than treatment with statins alone. In the safety analysis, treatment with statins alone was associated with a significant reduction in the numbers of total adverse events (RR = 0.665; 95% CI 0.539–0.819), liver-related adverse events (RR = 0.396; 95% CI 0.206–0.760) and kidney-related adverse events (RR = 0.146; 95% CI 0.075–0.285). Conclusion: We suggest that treatment with statins plus fibrates provides clinical benefits over treatment with statins alone but increased risks, especially of hepatic or renal side effects, should be monitored carefully.

Inhibitory effects of astaxanthin, β-cryptoxanthin, canthaxanthin, lutein, and zeaxanthin on cytochrome P450 enzyme activities.

Astaxanthin, β-cryptoxanthin, canthaxanthin, lutein and zeaxanthin, the major xanthophylls, are widely used in food, medicine, and health care products. To date, no studies regarding the inhibitory effects of these xanthophylls on the nine CYPs isozymes have been reported. This study investigated the reversible and time-dependent inhibitory potentials of five xanthophylls on CYPs activities in vitro. The reversible inhibition results showed that the five compounds had only a weak inhibitory effect on the nine CYPs. Lutein did not inhibit the nine CYPs activities. Astaxanthin weakly inhibited CYP2C19, with an IC₅₀ of 16.2 μM; and β-cryptoxanthin weakly inhibited CYP2C8, with an IC₅₀ of 13.8 μM. In addition, canthaxanthin weakly inhibited CYP2C19 and CYP3A4/5, with IC₅₀ values of 10.9 and 13.9 μM, respectively. Zeaxanthin weakly inhibited CYP3A4/5, with an IC₅₀ of 15.5 μM. However, these IC₅₀ values were markedly greater than the Cmax values reported in humans. No significant IC₅₀ shift was observed in the time-dependent inhibition screening. Based on these observations, it is unlikely that these five xanthophylls from the diet or nutritional supplements alter the pharmacokinetics of drugs metabolized by CYPs. These findings provide some useful information for the safe use of these five xanthophylls in clinical practice.

Pharmacokinetics of oltipraz in diabetic rats with liver cirrhosis

Background and purpose:  The incidence of diabetes mellitus is increased in patients with liver cirrhosis. Oltipraz is currently in trials to treat patients with liver fibrosis and cirrhosis induced by chronic hepatitis types B and C and is primarily metabolized via hepatic cytochrome P450 isozymes CYP1A1/2, 2B1/2, 2C11, 2D1 and 3A1/2 in rats. We have studied the influence of diabetes mellitus on pharmacokinetics of oltipraz and on expression of hepatic, CYP1A, 2B1/2, 2C11, 2D and 3A in rats with experimental liver cirrhosis.

Factors affecting the apparent clearance of tacrolimus in Korean adult liver transplant recipients.

Study Objective. To identify the factors affecting tacrolimus apparent total body clearance (Cl/F [F = bioavailability]) in adult liver transplant recipients.

Patterns of Adverse Drug Reactions in Different Age Groups: Analysis of Spontaneous Reports by Community Pharmacists.

Purpose To evaluate the clinical manifestations and causative drugs associated with adverse drug reactions (ADRs) spontaneously reported by community pharmacists and to compare the ADRs by age. Methods ADRs reported to the Regional Pharmacovigilance Center of the Korean Pharmaceutical Association by community pharmacists from January 2013 to June 2014 were included. Causality was assessed using the WHO-Uppsala Monitoring Centre system. The patient population was classified into three age groups. We analyzed 31,398 (74.9%) ADRs from 9,705 patients, identified as having a causal relationship, from a total pool of 41,930 ADRs from 9,873 patients. Median patient age was 58.0 years; 66.9% were female. Results Gastrointestinal system (34.4%), nervous system (14.4%), and psychiatric (12.1%) disorders were the most frequent symptoms. Prevalent causative drugs were those for acid-related disorders (11.4%), anti-inflammatory products (10.5%), analgesics (7.2%), and antibacterials (7.1%). Comparisons by age revealed diarrhea and antibacterials to be most commonly associated with ADRs in children (p < 0.001), whereas dizziness was prevalent in the elderly (p < 0.001). Anaphylactic reaction was the most frequent serious event (19.7%), mainly associated with cephalosporins and non-steroidal anti-inflammatory drugs. Among 612 ADRs caused by nonprescription drugs, the leading symptoms and causative drugs were skin disorders (29.6%) and non-steroidal anti-inflammatory drugs (16.2%), respectively. Conclusions According to the community pharmacist reports, the leading clinical manifestations and causative drugs associated with ADRs in outpatients differed among age groups.

Optimizing EEMCO guidance for the assessment of dry skin (xerosis) for pharmacies

People with dry skin (xerosis) are common in community pharmacies, but there is no consistent guidance for community pharmacists to evaluate and alleviate dry skin. Through evaluating any difference of the clinical scoring systems of EEMCO guidance between a dermatologist and pharmacists and the efficacy of moisturizers for the treatment of dry skin recommended by community pharmacists, we aim to validate a dry skin guidance through the help of community pharmacists. These results provide insight into how community pharmacists can help patients with dry skin.