Protective Effects of Shichimotsu-koka-To on Irreversible Thy-1 Nephritis

Abstract

Oxidative stress and peritubular capillary (PTC) injury are involved in the progression of chronic kidney disease (CKD). We investigated protective effects of Shichimotsu-koka-To (SKT), a Japanese traditional Kampo prescription, against nephrosclerosis and hypertension on a CKD model due to irreversible nephritis. Six-week-old male Wistar rats were subjected to uninephrectomy, and to injection of rabbit anti-thymocyte serum. SKT treatment was continued for 15 weeks, blood pressure was measured, and then renal specimens were collected. PTC networks were detected by immunostaining for CD-31. And superoxide dismutase (SOD)-like activity in the tissue was evaluated. Blood pressure in the SKT group, as well as sham group, was significantly lower than with the vehicle. SKT markedly ameliorated renal function, which was evaluated with urea nitrogen clearance. Compared with the vehicle, SKT treatment lowered both the glomerular enlargement and hyper-cellularity by 80%, and decreased the extracellular matrix area by 75%. SKT treatment also suppressed tubular injury, and maintained PTC networks. Furthermore, SKT recovered SOD-like activity to the basal levels. These results suggest that SKT may be useful for the treatment of CKD during the progression to nephrosclerosis, through the mechanisms of anti-oxidative activity and maintenance of PTC networks.Key words hypertension; glomerular hypertrophy; peritubular capillary; chronic kidney disease; oxidative stressThe number of patients with end-stage renal failure undergoing dialysis is increasing worldwide. Recently, it has been accepted that patients with chronic kidney disease (CKD) also develop cardiovascular diseases, with increased risks of death, cardiovascular events, and hospitalization. 1) Improvement of the clinical outcomes of CKD patients is therefore important. In Japan, chronic glomerulonephritis and nephrosclerosis are major causes of renal failure after diabetic nephropathy, which is the most common cause.2) Hypertension is an important symptom which influences the outcome of CKD, and angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) are beneficial to protect against renal injury in CKD.3)The herbal formula Shichimotsu-koka-To (SKT; Table 1) has occasionally been prescribed to treat hypertensive patients. 4)SKT was used for non-obesity hypertensive patients, and those complaining of the sensation of a rush of blood to the head, shoulder stiffness, tinnitus, and dull headache; however, in the last two or three decades, abundant new strong antihypertensive drugs have become available, and SKT has been used less. Recently, reevaluation of SKT treatment in combination with ACE-Is/ARBs drugs in CKD has begun. 5) In basic studies, SKT had an anti-hypertensive effect in Dahl strain rats.6) Enhanced serum NO x levels, and anti-oxidant activity through increasing superoxide dismutase (SOD)-like activity in the kidney by SKT were reported. 7,8) Previously, in a rat model of hypertensive nephrosclerosis induced by 5/6 nephrec...

An effective case of shichimotsukokato treatment for postherpetic neuralgia in a patient with chronic kidney disease

“…The effectiveness of shichimotsukokato in this case may be due to the amelioration of potential kekkyo . In addition to this, it has been reported that shichimotsukokato has a protective effect against renal dysfunction associated with hypertension and nephritis [8,9]. In this case, the patient had severe renal dysfunction associated with ANCA‐associated nephritis and hypertension.…”