Background: Ganoderma lucidum (Ganoderma or lingzhi) is widely used as an alternative medicine remedy to promote health and longevity. Recent studies have indicated that components extracted from Ganoderma have a wide range of pharmacological actions including suppressing inflammation and scavenging free radicals. We recently reported that tubular secretion of interleukin-8 (IL-8) induced by albumin is important in the pathogenesis of tubulointerstitial injury in the proteinuric state. In this study, we explored the protective effect of Ganoderma extract (LZ) on albumin-induced kidney epithelial injury.
Methods: Growth arrested human proximal tubular epithelial cells (PTECs) were incubated with 0.625 to 10 mg/ml human serum albumin (HSA) for up to 72 h. HSA induced DNA damage and apoptosis in PTEC in a dose- and time-dependent manner. Co-incubation of PTEC with 4-64 microg/ml LZ significantly reduced the oxidative damage and cytotoxic effect of HSA in a dose-dependent manner (P<0.001). Increased release of IL-8 and soluble intercellular adhesion molecules-1 (sICAM-1) in PTEC induced by HSA was ameliorated by co-incubation with Ganoderma (16 microg/ml). To explore the components of LZ that exhibited most protective effect in HSA-induced PTEC damages, LZ was further separated into two sub-fractions, LZF1 (MW <30 kDa) and LZF2 (MW <3 kDa), by molecular sieving using millipore membrane. PTEC were incubated with 5 mg/ml HSA in the presence of different doses of LZF1, LZF2 or unfractionated LZ.
Results: There was no difference in the degree of protection from HSA-induced cytotoxicity or oxidative DNA damage between different fractions of LZ. However, low molecular weight LZ (<3 kDa) was most effective in reducing sICAM-1 released from HSA-activated PTEC whereas the high molecular weight LZ (unfractionated LZ) was more effective in diminishing IL-8 production.
Conclusions: Our results suggest that Ganoderma significantly reduces oxidative damages and apoptosis in PTEC induced by HSA. The differential reduction of IL-8 or sICAM-1 released from HSA-activated PTEC by different components of the LZ implicates that components of Ganoderma with different molecular weights could play different roles and operate different mechanisms in preventing HSA-induced PTEC damage.