Negative control (NC) for Zn(II) Protoporphyrin

[1]. Heme oxygenase-1 in tumors: is it a false friend?. Antioxid Redox Signal. 2007;9(12):2099-2117.

[2]. Heme oxygenase and the cardiovascular-renal system. Free Radic Biol Med. 2005;39(1):1-25.

[3]. Heme oxygenase-mediated increases in adiponectin decrease fat content and inflammatory cytokines tumor necrosis factor-alpha and interleukin-6 in Zucker rats and reduce adipogenesis in human mesenchymal stem cells. J Pharmacol Exp Ther. 200.

Heme oxygenase-1 (HO-1) catalyzes the oxidation of heme to biologically active products: carbon monoxide (CO), biliverdin, and ferrous iron. It participates in maintaining cellular homeostasis and plays an important protective role in the tissues by reducing oxidative injury, attenuating the inflammatory response, inhibiting cell apoptosis, and regulating cell proliferation. HO-1 is also an important proangiogenic mediator. Most studies have focused on the role of HO-1 in cardiovascular diseases, in which its significant, beneficial activity is well recognized. A growing body of evidence indicates, however, that HO-1 activation may play a role in carcinogenesis and can potently influence the growth and metastasis of tumors. HO-1 is very often upregulated in tumor tissues, and its expression is further increased in response to therapies. Although the exact effect can be tissue specific, HO-1 can be regarded as an enzyme facilitating tumor progression. Accordingly, inhibition of HO-1 can be suggested as a potential therapeutic approach sensitizing tumors to radiation, chemotherapy, or photodynamic therapy. [1]

---

Heme oxygenase (HO) has been shown to be important for attenuating the overall production of reactive oxygen species (ROS) through its ability to degrade heme and to produce carbon monoxide (CO), biliverdin/bilirubin, and the release of free iron. Excess free heme catalyzes the formation of ROS, which may lead to endothelial cell (EC) dysfunction as seen in numerous pathological conditions including hypertension and diabetes, as well as ischemia/reperfusion injury. The upregulation of HO-1 can be achieved through the use of pharmaceutical agents, such as metalloporphyrins and some HMG-CoA reductase inhibitors. Among other agents, atrial natriretic peptide and donors of nitric oxide (NO) are important modulators of the heme-HO system, either through induction of HO-1 or the biological activity of its products. Gene therapy and gene transfer, including site- and organ-specific targeted gene transfer, have become powerful tools for studying the potential role of HO-1/HO-2 in the treatment of various cardiovascular diseases as well as diabetes. HO-1 induction by pharmacological agents or gene transfer of human HO-1 into endothelial cells (ECs) in vitro increases cell-cycle progression and attenuates Ang II, TNF-, and heme-mediated DNA damage; administration in vivo acts to correct blood pressure elevation following Ang II exposure. Moreover, site-specific delivery of HO-1 to renal structures in spontaneously hypertensive rats (SHR), specifically to the medullary thick ascending limb of the loop of Henle (mTALH), has been shown to normalize blood pressure and provide protection to the mTAL against oxidative injury. In other cardiovascular situations, delivery of human HO-1 to hyperglycemic rats significantly lowers superoxide (O(2)(-)) levels and prevents EC damage and sloughing of vascular EC into the circulation. In addition, administration of human HO-1 to rats in advance of ischemia/reperfusion injury considerably reduces tissue damage. The ability to upregulate HO-1 through pharmacological means or through the use of gene therapy may offer therapeutic strategies for cardiovascular disease in the future. This review discusses the implications of HO-1 delivery during the early stages of cardiovascular system injury or in early vascular pathology and suggests that pharmacological agents that regulate HO activity or HO-1 gene delivery itself may become powerful tools for preventing the onset or progression of certain cardiovascular pathologies. [2]

---

Adiponectin, an abundant adipocyte-derived plasma protein that modulates vascular function in type 2 diabetes, has been shown to provide cytoprotection to both pancreatic and vascular systems in diabetes. Therefore, we examined whether up-regulation of heme oxygenase (HO)-1 ameliorates the levels of inflammatory cytokines and influences serum adiponectin in Zucker fat (ZF) rats. ZF rats displayed a decrease in both HO activity and HO-1 and HO-2 protein levels and an increase in tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 compared with Zucker lean (ZL) rats. Treatment of ZF animals with 2 mg/kg cobalt protoporphyrin IX (CoPP) increased protein levels of HO-1 and HO activity, but HO-2 was unaffected. The increase in HO-1 was associated with a decrease in superoxide levels (p < 0.05) and an increase in plasma adiponectin (p < 0.005), compared with untreated ZF rats. CoPP treatment decreased visceral and s.c. fat content, and it reduced weight gain (p < 0.01). In addition, the inflammatory cytokines TNF-alpha and IL-6 were decreased (p < 0.04 and p < 0.008, respectively). Treatment of human bone marrow-derived adipocytes cultured with CoPP resulted in an increase in HO-1 and a decrease in superoxide levels. Up-regulation of HO-1 caused adipose remodeling, smaller adipocytes, and increased adiponectin secretion in the culture medium of human bone marrow-derived adipocytes. In summary, this study demonstrates that the antiobesity effect of HO-1 induction results in an increase in adiponectin secretion, in vivo and in vitro, a decrease in TNF-alpha and IL-6, and a reduction in weight gain. These findings highlight the pivotal role and symbiotic relationship of HO-1 and adiponectin in the modulation of the metabolic syndrome phenotype. [3]

C34H32CUN4O4

624.19

623.172

C, 65.42; H, 5.17; Cu, 10.18; N, 8.98; O, 10.25

14494-37-2

Mg(II) protoporphyrin IX;14947-11-6;Mn(II) protoporphyrin IX;21393-64-6;Ni(II) protoporphyrin IX;15415-30-2;Ga(III) protoporphyrin IX;222556-71-0;Cr(III) protoporphyrin IX;84640-43-7;Cd(II) protoporphyrin IX;80216-25-7;Pt(II) protoporphyrin IX;98303-94-7

3500653

Brown to reddish brown solid powder

2.322

94.32

2

8

8

43

1580

0

CC1=C(C2=CC3=NC(=CC4=C(C(=C([N-]4)C=C5C(=C(C(=N5)C=C1[N-]2)C)C=C)C)C=C)C(=C3CCC(=O)O)C)CCC(=O)O.[Cu+2]

ASFPSNQTLAUXFI-UHFFFAOYSA-L

InChI=1S/C34H34N4O4.Cu/c1-7-21-17(3)25-13-26-19(5)23(9-11-33(39)40)31(37-26)16-32-24(10-12-34(41)42)20(6)28(38-32)15-30-22(8-2)18(4)27(36-30)14-29(21)35-25;/h7-8,13-16H,1-2,9-12H2,3-6H3,(H4,35,36,37,38,39,40,41,42);/q;+2/p-2

copper;3-[18-(2-carboxyethyl)-7,12-bis(ethenyl)-3,8,13,17-tetramethylporphyrin-21,23-diid-2-yl]propanoic acid

cu(ii) protoporphyrin ix; 14494-37-2; cu(ii)protoporphyrinix; G91025; Cuprate(2-),[7,12-diethenyl-3,8,13,17-tetramethyl-21H,23H-porphine-2,18-dipropanoato(4-)-kN21,kN22,kN23,kN24]-, dihydrogen, (SP-4-2)-

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

---

注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

View More

注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

---

口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

View More

口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

---

注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

---

请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。