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. 2013 Jul 30;21(4):290-8.
doi: 10.4062/biomolther.2013.040.

Effects of Calcium Gluconate, a Water Soluble Calcium Salt on the Collagen-Induced DBA/1J Mice Rheumatoid Arthritis

Ki Cheul Sohn  1 , Su Jin Kang, Joo Wan Kim, Ki Young Kim, Sae Kwang Ku, Young Joon Lee
Affiliations

Effects of Calcium Gluconate, a Water Soluble Calcium Salt on the Collagen-Induced DBA/1J Mice Rheumatoid Arthritis

Ki Cheul Sohn et al. Biomol Ther (Seoul). .

Abstract

This study examined the effects of calcium (Ca) gluconate on collagen-induced DBA mouse rheumatoid arthritis (CIA). A single daily dose of 200, 100 or 50 mg/kg Ca gluconate was administered orally to male DBA/1J mice for 40 days after initial collagen immunization. To ascertain the effects administering the collagen booster, CIA-related features (including body weight, poly-arthritis, knee and paw thickness, and paw weight increase) were measured from histopathological changes in the spleen, left popliteal lymph node, third digit and the knee joint regions. CIA-related bone and cartilage damage improved significantly in the Ca gluconate- administered CIA mice. Additionally, myeloperoxidase (MPO) levels in the paw were reduced in Ca gluconate-treated CIA mice compared to CIA control groups. The level of malondialdehyde (MDA), an indicator of oxidative stress, decreased in a dosedependent manner in the Ca gluconate group. Finally, the production of IL-6 and TNF-α, involved in rheumatoid arthritis pathogenesis, were suppressed by treatment with Ca gluconate. Taken together, these results suggest that Ca gluconate is a promising candidate anti-rheumatoid arthritis agent, exerting anti-inflammatory, anti-oxidative and immunomodulatory effects in CIA mice.

Keywords: Anti-inflammation; Anti-oxidation; Calcium gluconate; Immunomodulation; Rheumatoid arthritis.

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Figures

Fig. 1.
Fig. 1.. Ca gluconate inhibited changes in body weight in CIA mice. Values are expressed as means ± SD (n=8). ***p<0.001 compared with the mean body weights at immunization. -1IM: 1 day before immunization, IM: immunization (start of administration of test materials); 23, day of antigen challenge. All animals were fasted overnight before immunization and sacrifice (40 days after immunization).
Fig. 2.
Fig. 2.. Ca gluconate reduced clinical arthritis scores, and paw and knee thickness in Ca gluconate-treated CIA mice. (A) Significant decreases in clinical arthritis scores were detected in Ca gluconatetreated mice (B) Paw thickness was significantly (p<0.01 or p<0.05) reduced in Ca gluconate-treated mice (a, b) compared with CIA control mice. (C) Knee thickness was significantly (p<0.01 or p<0.05) reduced in Ca gluconate-treated mice (a, b) compared with CIA control mice. Values are expressed as means ± SD (n=8). AC; day of antigen challenge at 23 days after immunization. All animals were fasted overnight before immunization.
Fig. 3.
Fig. 3.. Ca gluconate had a therapeutic effect on the CIA mice mediated by anti-inflammatory, anti-oxidative and immunomodulatory effects. (A) Paw MPO and MDA contents of Ca gluconate-treated mice were lower compared to CIA control mice. (B) Paw TNF-α and IL-6 levels in Ca gluconate-treated mice were lower compared with CIA control mice. (C) Splenocyte TNF-α and IL-6 levels in Ca gluconatetreated mice were lower compared with CIA control mice. Values are expressed as means ± SD (n=8). ap<0.01 and bp<0.05 as compared with the intact control; cp<0.01 and dp<0.05 as compared with the CIA control.
Fig. 4.
Fig. 4.. Histopathological profiles of the knee in the intact control (A-D), CIA control (E-H), ENBREL group (I-L), Ca gluconate-treated groups; 200 mg/kg (M-P), 100 mg/kg (Q-T) and 50 mg/kg (U-X). Marked decreases in the articular surfaces (cartilage and bone) were detected in the knee articular surfaces of the femur and tibia, with severe inflammatory cell infiltration into the synovial cavity in the CIA control mice. However, histopathological changes in the CIA group were decreased dramatically by treatment with Ca gluconate. The arrow indicates articular surface thickness. Dotted arrow indicates articular cartilage thickness. All were stained with H&E. Scale bars=160 μm.
Fig. 5.
Fig. 5.. Histopathological profiles of the third digits in the intact control (A-C), CIA control (D-F), ENBREL group (G-I), Ca gluconatetreated groups; 200 mg/kg (J-L), 100 mg/kg (M-O) and 50 mg/kg (PR). Marked edematous changes, inflammatory cell infiltration and erosive damage of digital bones were detected on the third digits of the CIA control mice. However, these histopathological changes were decreased dramatically by treatment with Ca gluconate. The arrow indicates the dorsum paw skin thickness. Doted arrow indicates cortical bone thickness. All were stained with H&E. Scale bars=160 μm.
Fig. 6.
Fig. 6.. Ca gluconate ameliorated the histopathological changes of the knee and third digit. (A) The semiquantitative scores of Ca gluconate- treated mice were lower compared with the CIA control mice. (B) The knee articular surface thickness of Ca gluconate-treated mice was greater compared with the CIA control mice. Knee articular surface thicknesses are shown in Fig. 4 (arrow). (C) The knee articular cartilage thickness of Ca gluconate-treated mice was greater compared with the CIA control mice. Knee articular cartilage thicknesses are shown in Fig. 4 (dotted arrow). (D) Infiltrated inflammatory cells of Ca gluconate-treated mice were lower compared with the CIA control mice (E). Increases in the third digit dorsum pedis skin thickness and decreases in the cortical bone thickness were inhibited by treatment with Ca gluconate compared with the CIA control mice. Measurements of the third digit dorsum pedis skin (arrow) and cortical bone (dotted arrow) thicknesses are shown in Fig. 5. Values are expressed as means ± SD (n=8); ap<0.01 and bp<0.01 as compared with the intact control; cp<0.01 and dp<0.05 as compared with the CIA control.
Fig. 7.
Fig. 7.. Histopathological profiles of the spleen in the intact control (A, B), CIA control (C, D), ENBREL group (E, F), Ca gluconate-treated groups; 200 mg/kg (G, H), 100 mg/kg (I, J) and 50 mg/kg (K, L). Marked enlargement of the spleen, related to hyperplasia of lymphoid cells in the white pulp, was detected in the CIA control mice. However, these histopathological changes decreased dramatically after treatment with ENBREL and all three doses of Ca gluconate. Arrow indicates the total spleen thickness. Doted arrow indicates white pulp. All were stained with H&E. Scale bars=160 μm.
Fig. 8.
Fig. 8.. Histopathological profiles of the left popliteal lymph nodes in the intact control group (A, B), CIA control group (C, D), ENBREL group (E, F), and Ca gluconate-treated groups; 200 mg/kg (G, H), 100 mg/kg (I, J) and 50 mg/kg (K, L). Marked enlargement of popliteal lymph nodes, related to hyperplasia of lymphoid cells in the cortex of the lymph nodes, was detected in the CIA control mice. However, these histopathological changes decreased dramatically after treatment with ENBREL and all three doses of Ca gluconate. Arrow indicates the total popliteal lymph node thickness. Doted arrow indicates cortex thicknesses. All were stained with H&E. Scale bars=160 μm.
Fig. 9.
Fig. 9.. Ca gluconate improved the histopathological changes of the secondary lymphatic organs. (A) The total spleen and white pulp thicknesses of Ca gluconate-treated mice were significantly decreased compared with the CIA control mice. Measurements of total spleen (arrow) and white pulp (dotted arrow) thicknesses are shown in Fig. 7. (B) The splenic white pulp of Ca gluconate-treated mice was significantly lower compared with CIA control mice. (C) The popliteal lymph node total and cortex thickness of Ca gluconate-treated mice were significantly lower compared with the CIA control mice. Measurement of lymph node total (arrow) and cortex (dotted arrow) thicknesses are shown in Fig. 8. Values are expressed as means ± SD (n=8); ap<0.01 and bp<0.05 compared with the intact control; cp<0.01 and dp<0.05 compared with the CIA control.
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