*2.5. Lipid Peroxidation*

The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) of the kidney tissue were measured in all groups. The MDA production was increased in kidney tissue of adriamycin-treated model rats (Table 6). While adriamycin treatment decreased the SOD level of the kidney tissue of rats. Treating adriamycin-induced rats with LMWF significantly and dose-dependently increased the SOD level and decreased the MDA level in kidney tissue. Fucoidan treatment also increased the SOD level and decreased the MDA level. LMWF at the dose of 100 mg/kg was more potent in decreasing the MDA level (*p* < 0.05), while both fucoidan and LMWF had similar activities on SOD at the same dose (100 mg/kg).


**Table 6.** Effect of fucoidan and low molecular weight fucoidan (LMWF) on malondialdehyde (MDA) and superoxide dismutase (SOD) levels in kidney ( *X* ± *S*).

> : *p* < 0.05 (vs normal group); \*: *p* < 0.05, \*\*: *p* < 0.01 (vs model group).

MDA is a main marker of endogenous lipid peroxidation [24]. The increase of MDA production indicates that peroxidative damage increases after adriamycin induction. Antioxidant enzymes are considered to be a primary defense that prevents biological macromolecules from oxidative damage. SOD is an important enzymatic antioxidant defense mechanisms that protects against oxidative processes initiated by the superoxide anion.

The results demonstrated that both fucoidan and its depolymerized fragment were successful in inhibiting lipid peroxidation in the kidney of adriamycin-induced rats, as observed in the reduction of MDA production and increase of SOD level. The results were in accordance with previous studies on the antioxidant activities of fucoidan and low-molecular-weight fucoidans [24]. The renoprotective effect of fucoidans was at least partly due to its antioxidant activities.

#### *2.6. E*ff*ect of Molecular Weight on Adriamycin-Induced Nephrotic Syndrome*

The molecular weight has been demonstrated to play an important role in the biological activities of polysaccharides [25]. Low-molecular-weight heparin is a classic example. Comparing with unfractioned heparin, low-molecular-weight heparin has improved bio-availability, a longer half-life, and more predictable dose response, which make its use increasingly common in the treatment and prophylaxis of thromboembolism [18]. High and low-molecular-weight fucoidans were also reported to have di fferential e ffect on the severity of collagen-induced arthritis in mice [26]. A daily oral administration of high-molecular-weight fucoidan (HMWF, 100 ± 4 kDa) enhanced the severity of arthritis, inflammatory responses in the joint cartilage, and the levels of collagen-specific antibodies, while low-molecular-weight fucoidan (LMWF, 1 ± 0.2 kDa) reduced the severity of arthritis and the levels of Th1-dependent collagen-specific IgG2a.

Our group previously reported that fucoidan from *S. japonica* has a protective e ffect on chronic renal failure, diabetic nephropathy, and acute kidney injury [8–11]. This study revealed that fucoidan and low-molecular-weight fucoidan also have a protective e ffect on adriamycin-induced nephrotic syndrome. LMWF at the same dose had a better protective e ffect than fucoidan. Since fucoidan and LMWF had similar sugar constituents but di fferent molecular weight, the di fference in renoprotection between fucoidan and LMWF was mainly attributed to their discrepancy in molecular weight. The exact mechanism of the renoprotective e ffect of fucoidan and LMWF needs further investigation in the following study.
