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 into biologically active products: carbon monoxide (CO), biliverdin, and ferrous ions. It participates in maintaining cellular homeostasis and plays a vital protective role in tissues by reducing oxidative damage, attenuating inflammatory responses, inhibiting apoptosis, and regulating cell proliferation. HO-1 is also an important pro-angiogenic mediator. Most research focuses on the role of HO-1 in cardiovascular disease, and its significant beneficial activity is widely recognized. However, mounting evidence suggests that HO-1 activation may play a role in tumorigenesis and significantly affect tumor growth and metastasis. HO-1 is frequently upregulated in tumor tissues, and its expression further increases after treatment. Although its exact role may be tissue-specific, HO-1 can be considered an enzyme that promotes tumor progression. Therefore, inhibiting HO-1 could be considered a potential therapeutic approach that could enhance tumor sensitivity to radiotherapy, chemotherapy, or photodynamic therapy. [1]

---

Heme oxygenase (HO) has been shown to be crucial in reducing the overall production of reactive oxygen species (ROS) through the degradation of heme and the generation of carbon monoxide (CO), biliverdin/bilirubin, and the release of free iron. Excess free heme catalyzes the generation of ROS, which can lead to endothelial cell (EC) dysfunction, a condition seen in a variety of pathological conditions, including hypertension, diabetes, and ischemia/reperfusion injury. Upregulation of HO-1 can be achieved using drugs such as metalloporphyrins and certain HMG-CoA reductase inhibitors. In addition, atrial natriuretic peptide and nitric oxide (NO) donors are also important regulators of the heme-HO system, exerting their effects by inducing the bioactivity of HO-1 or 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 and diabetes. In vitro experiments have shown that inducing HO-1 expression through drugs or transferring the human HO-1 gene into endothelial cells (ECs) can promote cell cycle progression and alleviate angiotensin II (Ang II), tumor necrosis factor (TNF-α), and heme-mediated DNA damage; in vivo administration can correct the hypertension induced by Ang II exposure. Furthermore, in spontaneously hypertensive rats (SHR), specific delivery of HO-1 to renal structures, particularly the thick ascending limb of the loop of Henle in the medulla (mTALH), has been shown to normalize blood pressure and protect mTAL from oxidative damage. In other cardiovascular diseases, delivery of human HO-1 to hyperglycemic rats significantly reduces superoxide (O₂⁻) levels and prevents endothelial cell damage and detachment into the bloodstream. Moreover, injection of human HO-1 into rats before ischemia/reperfusion injury significantly reduces tissue damage. The ability to upregulate HO-1 through drug or gene therapy may provide new strategies for the treatment of cardiovascular diseases in the future. This review explores the significance of delivering HO-1 in the early stages of cardiovascular injury or early vascular lesions, and points out that drugs that regulate HO activity or HO-1 gene delivery itself may become powerful tools for preventing the occurrence or progression of certain cardiovascular diseases. [2] Adiponectin is a plasma protein abundant from adipocytes that can regulate vascular function in type 2 diabetes and has been shown to have cytoprotective effects on both the pancreas and vascular system in diabetes. Therefore, we investigated whether upregulating heme oxygenase (HO)-1 could improve the levels of inflammatory cytokines in Zucker obese (ZF) rats and affect serum adiponectin levels. Compared with Zucker lean rats (ZL), ZF rats had decreased heme oxygenase (HO) activity and HO-1 and HO-2 protein levels, while tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were increased. After treatment of ZF rats with 2 mg/kg cobalt protoporphyrin IX (CoPP), HO-1 protein levels and HO activity were increased, but HO-2 levels were not affected. Compared with untreated ZF rats, the increase in HO-1 level was associated with the decrease in superoxide level (p < 0.05) and the increase in plasma adiponectin level (p < 0.005). CoPP treatment reduced visceral and subcutaneous fat content and reduced weight gain (p < 0.01). In addition, the levels of inflammatory cytokines TNF-α and IL-6 were also reduced (p < 0.04 and p < 0.008, respectively). HO-1 expression increased and superoxide level decreased after treatment of cultured human bone marrow-derived adipocytes with CoPP. The upregulation of HO-1 led to adipose tissue remodeling, adipocyte volume reduction, and increased adiponectin secretion in human bone marrow-derived adipocyte culture medium. In summary, this study showed that the anti-obesity effect induced by HO-1 was manifested by increased adiponectin secretion, decreased TNF-α and IL-6 levels, and reduced weight gain in vivo and in vitro. These findings highlight the key roles of HO-1 and adiponectin in the regulation of metabolic syndrome phenotypes and their symbiotic relationship. [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

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

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

---

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

 (Please use freshly prepared in vivo formulations for optimal results.)