*2.4. Blood Biochemical Indexes*

At the end of the experiment, the blood biochemical indexes of rats were detected. The blood levels of total protein (TP), albumin, blood urea nitrogen (BUN), serum creatinine (SCr), total cholesterol (TC), and total triglyceride (TG) of the model rats were significantly changed (Table 5). It is worth noting that the blood lipid level of the model rats was remarkably elevated. Compared with the normal rats, the blood level of total cholesterol and total triglyceride of the model rats induced by adriamycin were increased by 9.4-fold and 6.4-fold, respectively. These results indicated that adriamycin treatment could induce significant hyperlipidemia.

**Table 5.** Effect of fucoidan and low molecular weight fucoidan (LMWF) on blood biochemical indexes of NS rats (*X* ± *S*).


: *p* < 0.05, : *p* < 0.01 (vs normal group); \*: *p* < 0.05, \*\*: *p* < 0.01 (vs model group). T-P: total protein; ALB: albumin; SCr: serum creatinine; BUN: blood urea nitrogen; TG: triglyceride; T-CHO: total cholesterol.

Blood urea nitrogen and serum creatinine are two major indexes of renal function. As expected, adriamycin-induced rats had higher BUN and SCr levels, indicating that the kidney of the model rats was damaged by adriamycin administration. Blood total protein and albumin level of model rats were decreased by adriamycin, suggesting that hypoalbuminemia occurred in the model rats. However, the alteration of these biochemical indexes could be significantly reversed by fucoidan and LMWF treatment in a dose-dependent manner. Fucoidan, dexamethasone and LMWF (50 mg/kg) decreased the levels of BUN and SCr at the similar magnitude, while LMWF at the dose of 100 mg/kg had the highest decrease in SCr level (*p* < 0.05, vs fucoidan group). Both fucoidan and LMWF could significantly increase the blood albumin level and decrease TG and TC levels, and LMWF at the dose of 100 mg/kg had a more potent activities (*p* < 0.05). But the positive control dexamethasone could not alter the level of blood albumin, TG, and TC.

These results showed that both fucoidan and its depolymerized fragment could improve the renal function, elevate blood albumin level, and inhibit hyperlipidemia. Low-molecular-weight fucoidan had a more potent activity.

Adriamycin is a kind of amino nucleoside substance. After adriamycin transformed to semiquinone free radicals in organism, the radicals can react with oxygen to produce reactive oxygen species (ROS). The ROS further induces lipid peroxidation of glomerular epithelial cells and destroys the structure and function of the filtration membrane, leading to proteinuria and subsequent nephrotic syndrome [4]. It has been observed that a high cholesterol diet can aggravate the lipid metabolism disorder of adriamycin-induced renal injury [22]. On the contrary, serious proteinuria could lead to the incidence of hypoproteinemia, which further causes malnutrition, especially protein malnutrition. Hypoproteinemia can also reduce the plasma osmotic pressure, especially the colloidal osmotic pressure around the hepatocytes, stimulate the hepatocytes to synthesize lipoproteins, and finally results in the disorder of lipid metabolism and hyperlipidemia.

The renoprotective e ffect of fucoidan or LMWF may be due to its antioxidant activity. Fucoidan and low-molecular-weight fucoidan were proved to have in vitro free radical scavenging activities [23]. The antioxidant activity of fucoidan may be helpful in eliminating the reactive oxygen species initiated by adriamycin and maintaining the structure and function of glomerular basement membrane, thus inhibiting the occurrence and development of proteinuria. In order to verify the correlation between the renoprotection and anti-oxidation of fucoidan and its depolymerized fragment, we further detected the lipid peroxidation in kidney of rats.
