Isohumulones derived from hops ameliorate renal injury via an anti-oxidative effect in Dahl salt-sensitive rats.
Previous studies have reported that isohumulones, the bitter compounds in beer, improve insulin resistance and hyperlipidemia in several animal models. In this study, we examined whether isohumulones ameliorate renal injury. Dahl salt-sensitive hypertensive rats were fed a low-salt diet (LS), a high-salt diet (HS) or a high-salt diet containing 0.3% isohumulones (HS+IH) for 4 weeks. Urinary nitrite/nitrate (NOx) excretion was measured at 4 weeks along with blood pressure and urinary protein excretion. Renal injury was evaluated histologically and reactive oxygen species (ROS) and nitric oxide (NO) production in the renal cortex was visualized. Oxidative stress and NO synthase (NOS) expression were evaluated by immunohistochemical staining and Western blot analysis. Mean blood pressure was significantly decreased in the HS+IH group compared with the HS group at 4 weeks (158.1+/-8.7 vs. 177.5+/-3.7 mmHg; p<0.05). Isohumulones prevented the development of proteinuria in the HS+IH group compared with the HS group at 2 weeks (61.7+/-26.8 vs. 117.2+/-9.8 mg/day; p<0.05). Glomerulosclerosis and interstitial fibrosis scores were significantly decreased in the HS+IH group compared with the HS group (0.61+/-0.11 vs. 1.55+/-0.23, 23.7+/-6.8 vs. 36.1+/-3.5%; p<0.05 for both). In the HS group, increased ROS and decreased NO were observed in glomeruli in vivo. Isohumulones reduced the ROS production, leading to the restoration of bioavailable NO. Urinary NOx excretion was significantly increased in the HS+IH group compared with the HS group. Furthermore, renal nitrotyrosine was increased in the HS group compared with the LS group, and this effect was prevented by isohumulones. Renal NOS expression did not differ among the three groups. These results suggest that isohumulones may prevent the progression of renal injury caused by hypertension via an anti-oxidative effect.
Namikoshi
Tamehachi
T
Division of Nephrology, Department of Internal Medicine, Kawasaki Medical School, Japan.
Tomita
Naruya
N
Fujimoto
Sohachi
S
Haruna
Yoshisuke
Y
Ohzeki
Masahito
M
Komai
Norio
N
Sasaki
Tamaki
T
Yoshida
Aruto
A
Kashihara
Naoki
N
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure; D015153:Blotting, Western; D003517:Cyclopentanes / Q000494:pharmacology / Q000627:therapeutic use*; D027582:Humulus / Q000737:chemistry; D006973:Hypertension / Q000139:chemically induced / Q000150:complications*; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000652:urine; D019001:Nitric Oxide Synthase / Q000032:analysis; D009573:Nitrites / Q000652:urine; D018384:Oxidative Stress / Q000187:drug effects; D011507:Proteinuria; D051381:Rats; D020303:Rats, Inbred Dahl; D017382:Reactive Oxygen Species; D012965:Sodium Chloride / Q000633:toxicity; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D000975:Antioxidants; D003517:Cyclopentanes; D009566:Nitrates; D009573:Nitrites; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D012965:Sodium Chloride; C081209:isohumulone; D019001:Nitric Oxide Synthase