BPC-157 in the urinary and reproductive system. Peptide therapy in kidney diseases.

Abstract: The action of BPC-157 in the genitourinary system involves both preventive and nephroprotective treatment, as well as contributing to alleviating already existing disease states and mitigating their symptoms.

Keywords: urinary system; reproductive system; genitourinary system; kidney; ureter; urinary bladder; pelvis; uterus; rectum; urethra; kidney stones; vesicovaginal fistula; giant ureter; urinary incontinence; BPC-157 peptide therapy; experimental studies; method; ureteral stricture; scrotal injury; nephroprotection; disease

List of abbreviations: BPC-157-Body Protection Compound; LPP- Leak Point Pressure- intravesical pressure level;

Material and methods: The studies were conducted on laboratory animals, in this case male and female albino rats.

Genitourinary system

Structure of the genitourinary system

The most important component of the urinary system is the kidneys, which are paired organs whose parenchyma is made up of nephrons. Due to their rich blood supply, each kidney is supplied by a renal artery, which divides into upper, middle, and lower branches. The kidneys consist of the medulla and cortex, from which papillae enter the minor calyces and then the renal pelvises, forming another part of the system: the ureters. The ureters connect the kidneys to the urinary bladder, a reservoir located in the pelvis with a pubic symphysis at the back, while its front part varies depending on sex. In the female urogenital system, the uterus is located in front of the bladder, while in the male system, it is the rectum. Urine collected in the bladder is expelled through the urethra, which is longer in males than in females, and in both cases, the urethra connects with the genital organs, leading to the formation of the urogenital system. The urinary system also includes interlobar arteries that transition into arcuate arteries. For reference, let's recall the structure of the female and male urogenital systems. (Fig.1)

Figure 1. Structure of the male and female genitourinary system

Functions of the genitourinary system

The primary function of the urinary system is the excretion of all unnecessary and harmful metabolic waste products from the body, which is why it can be called the excretory system. Additionally, it participates in hormone production and maintains a constant level of bodily fluids. The basic function of the reproductive system is reproduction through the production of gametes and egg cells. The male reproductive organs primarily serve to produce semen containing sperm, while the female organs produce egg cells and hormones, also creating conditions for fertilization and fetal development within the maternal body.

Diseases of the genitourinary system

The human genitourinary system is exceptionally sensitive and prone to infections, which is why preventing diseases of this system is so important. Untreated diseases of the genitourinary system can lead to serious consequences and complications such as infertility and, in extreme cases, can threaten human life. To avoid disease phenomena and prevent their exacerbation, regular basic urine tests and therapies preventing their occurrence are important, protecting the genitourinary system from all kinds of infections and diseases, especially since they often have no initial symptoms, which complicates diagnosis and delays treatment. A modern method in the treatment of disorders and diseases of the genitourinary system is BPC-157 therapy. 

Therapy with the BPC-157 peptide for selected diseases of the genitourinary system

1.Urinary incontinence

Urinary incontinence is defined as a process in which urine leakage is uncontrolled and involuntary, for example during coughing, sneezing, or physical exertion. In the general classification, several degrees of urinary incontinence are distinguished, depending on the amount of uncontrolled urine leakage, including drop-level, mild, moderate, severe, and very severe. The most common cause of urinary incontinence is considered to be the weakening of the pelvic floor muscles, which are responsible for tightening the urethra and controlling urination. Symptoms occur in both women and men, but in women, due to procedures and surgeries performed in the pelvic area, natural childbirth, or hormonal changes, they occur more frequently. In men, urinary incontinence most often appears due to prostate enlargement. The condition can coexist with other diseases such as diabetes, Ehlers-Danlos syndrome, or chronic constipation. Pharmacological treatment is used in cases of urge urinary incontinence and is carried out with anticholinergic drugs. Surgical treatment is most often used in cases of stress urinary incontinence, for example by implanting an artificial sphincter. Conservative treatment involves, for example, electrical stimulation of the pelvic floor muscles or Kegel exercises, which are exercises for the pelvic floor muscles. Currently, BPC-157 therapy significantly improves the condition of these muscles, which results in a reduced risk of symptoms and their alleviation.

BPC-157 Peptide Therapy

Due to its mode of action, the BPC-157 peptide acts as a tissue-elasticizing agent, leading to strengthening of the pelvic floor muscles. As known from previous articles, the peptide also affects the nervous system, which in the case of urinary incontinence stops the sensation of bladder urgency. Regular and preventive therapy with the BPC-157 peptide leads to thickening of the urethral muscle structure, significantly reducing the risk of urinary incontinence in the future. The use of BPC-157 therapy leads to complete cure of urinary incontinence.

b. Conducted experimental studies

The study material consisted of female albino rats weighing from 310g to 350g. Study procedure:

The procedure was performed under deep anesthesia using ketamine administered intraperitoneally. Sharp dissection of the pelvic fascia was carried out, resulting in peripheral detachment of the proximal and distal urethra from the anterior vaginal wall and pubic bone. After the procedure, the control group was given saline and a catheter was inserted. The study group received the BPC-157 peptide for seven days after the procedure. During the examination, bladder contractions and resulting leaks were observed by filling the bladder while simultaneously applying pressure to release fluid at the urethral opening. After measurements were completed, the entire bladder and urethra were removed by excising the pubic symphysis, thus preserving the entire urethral segment. Changes within the segment were observed using specialized computer programs connected to a microscope.

Results

BPC-157 peptide therapy, regardless of the dosing regimen or method of administration, completely counteracts the decrease in LPP values, i.e., the height of intravesical pressure. Thanks to the action of BPC-157, primary values recorded in healthy rats were achieved. Additionally, the urethral wall treated with BPC-157 shows a thicker and more regular muscular structure, while the control group is characterized by the presence of a thin muscle layer.

  Conclusions

The above results indicate that the action of BPC-157, compared to the control, has a regenerative effect on urethral damage and, when used during conservative treatment, leads to a reduction in the likelihood of urinary incontinence symptoms.

2. Vesicovaginal Fistula

A vesicovaginal fistula is a condition often mistaken for the aforementioned urinary incontinence. The fistula forms due to damage to the thin wall of the urinary bladder, which, due to its anatomical structure, is located adjacent to the vagina. The most common cause of the disease is considered to be a complication after gynecological procedures. Other causes include cesarean section, bladder radiotherapy, or endometriosis lesions. Vesicovaginal fistulas can be simple or complex depending on the size of the channel. A symptom of fistula formation is the leakage of urine into the vagina accompanied by abdominal pain, intestinal obstruction, and hematuria. In acute and complex cases, treatment is usually surgical. In additional treatment cases, accelerating regeneration or preventive therapy, BPC-157 peptide therapy is used.

BPC-157 Peptide Therapy

Considering the studies below, BPC-157 therapy is a safe peptide profile, administered parenterally or orally to individuals with vesicovaginal fistulas. Under certain conditions, it may be one of the solutions in the wound healing process after fistula surgery. Vesicovaginal fistulas are associated with frequent intimate infections, discomfort, and gradually exclude patients from social life, which is why selecting an appropriate and safe therapy such as BPC-157 therapy is so important. In adjunctive treatment alongside surgical therapy, BPC-157 participates in postoperative regeneration of the vesicovaginal fistula. In preventive and regenerative treatment, in simple cases, it may prevent the occurrence and recurrence of this condition as well as treat it.

b. Conducted experimental studies

Material

Female rats weighing 200g and aged 8 to 10 weeks were used for the study.

Course of the study

The procedure was performed under deep anesthesia using intraperitoneally administered ketamine. A longitudinal incision was made in the posterior wall of the bladder and the anterior wall of the vagina, 4 mm in length, creating a vesicovaginal fistula using a single-layer technique with single sutures. BPC-157 was administered at doses of 10 μg/kg, 1 μg/kg, 100 ng/kg, and 10 ng/kg throughout the experiment, starting on day zero when therapy began, and daily during the trial periods of 7, 14, 21, 28, and 42 days. Control animals received an equivalent amount of saline. Immediately before euthanasia, under deep anesthesia, the fluid pressure required to cause fistula leakage was measured (biomechanical test). Differences in fistula healing between groups were observed via microscopic examination. During the study, daily observations were made for the presence of urine in the vagina, possible urinary incontinence, and the macroscopic appearance of the vagina and urethra. After euthanasia, the presence of adhesions, signs of infection, and healing of the fistula tissue on the bladder and vaginal sides were observed.

Results

After administration of the BPC-157 peptide at all doses (10 μg/kg, 1 μg/kg, 100 ng/kg, and 10 ng/kg), especially 14 days post-surgery, the diameter of the fistula opening was significantly reduced. Closure of the vesicovaginal fistula occurred in all rats treated with BPC-157 therapy after a 6-week peptide treatment period. Additionally, the study found no presence of urinary stones. In the control group, urinary stones and vesicovaginal fistulas were observed. Histological examination revealed visible collagenization and neovascularization causing closure of the tissue defect and alleviation of inflammation under the influence of BPC-157. 

Conclusions

Through the action of BPC-157 at doses of 10 μg/kg, 1 μg/kg, 100 ng/kg, and 10 ng/kg, healing of the vesicovaginal fistula in rats occurs, indicating that BPC-157 has a very strong protective effect by alleviating tissue damage and structural abnormalities caused by injury.

3. Ureteral Stricture

Ureteral stenosis, also called ureteropelvic junction obstruction, is a condition involving a defect of the ureter that leads to retention/stasis of urine above the stenosis. The flow of urine to the bladder, produced by the kidneys, is prevented due to improper ureter function. This process leads to urine retention in the kidney with simultaneous increase in intrarenal pressure, destruction of the renal parenchyma, and kidney failure resulting in hydronephrosis. Causes of ureteral stenosis include congenital defects of the smooth muscles of the ureter wall, abnormal ureteral blood supply, connective tissue adhesions, or vesicoureteral reflux. Hydronephrosis can occur in one or both kidneys, and symptoms vary accordingly. If hydronephrosis affects one kidney, symptoms include pain in the lumbar region, vomiting and nausea, or a positive Goldflam sign. Hydronephrosis in both kidneys is characterized by symptoms such as loss of appetite, weight gain, swelling of both lower limbs, or weakness and nausea. In cases of acute symptoms and disease progression, surgical treatment is recommended. In mild cases, specialized medications and precursor therapy with BPC-157 may be used to treat ureteral stenosis.

a. BPC-157 Therapy

Therapy with the BPC-157 peptide promotes proper function and operation of the ureter. The flow of urine to the bladder, produced by the kidneys, is enabled thanks to the action of the ureter. Through the action of BPC-157, intrarenal pressure is lowered, which significantly improves the condition and efficiency of the kidneys. Hydronephrosis caused by ureteral stenosis is inhibited or eliminated under the influence of the peptide. Preventive treatment with BPC-157 therapy leads to a reduced risk of ureteral stenosis formation in the future.

b. Conducted experimental studies

Material Male rats were used in the study.

Study course:

In rats, a procedure of ureter ligation was performed, which led to hydronephrosis, development of fibrosis, damage to tubular cells, and interstitial inflammation. After the injury, BPC-157 peptide was administered intraperitoneally at doses of 10 μg/kg and 10 ng/kg. In the control group, an equivalent amount of saline was used. The assessment of results was made at 24 and 96 hours after peptide administration and included changes in the kidneys on a scale from 0 to 3, where: 0 - healthy kidney, 1 - mild hydronephrosis, 2 - moderate hydronephrosis, visible dilation of the renal pelvis, few changes on the kidney surface, 3 - severe hydronephrosis, dilation of the renal pelvis, thinning of the renal parenchyma, and a significant number of changes on the kidney surface.

Results:

The action of the BPC-157 peptide causes a clear and advanced improvement in the condition of the ureter, observed both after 24 and 96 hours. Regular, severe hydronephrosis, dilation of the renal pelvis, and thinning of the kidney parenchyma were inhibited. Acute hydronephrosis was restored to a mild hydronephrosis state or completely eliminated.

Conclusions:

The action of BPC-157 peptide at doses of 10 μg/kg and 10 ng/kg causes the elimination of hydronephrosis, increased intrarenal pressure, or kidney failure, leading to the inhibition of ureteral stricture disease.

4. Scrotal Injury

Scrotal injury is classified as a blunt trauma, meaning injuries caused by contusion, damage due to occupational work, injuries acquired during accidents, assaults, or while practicing certain sports disciplines. Injuries can be open or closed. Open injuries occur when the continuity of the scrotal skin is broken. In cases of scrotal damage itself, skin defects most often occur. Closed injuries may present with swelling, tenderness, and bruising. In treatment, for scrotal skin defects, coverage with skin grafts from the perineal or thigh area is possible. For contusions and minor scrotal injuries, regenerative drug therapy is introduced, including BPC-157 peptide therapy.

a. BPC-157 Therapy

BPC-157 shows strong, beneficial, and regenerative effects on scrotal edema, which significantly subsided under the influence of the peptide. Regular use of BPC-157 peptide will lead to the alleviation of pain and swelling symptoms associated with scrotal injury. Treatment with BPC-157 is characterized by high efficacy and safety in its action profile and additionally prevents the growth and enlargement of scrotal injuries and edema.

5. Cystitis

Cystitis is recognized as an infection of the urinary tract caused by microorganisms present in it, which can multiply, leading to inflammation. Under normal conditions, the urinary tract above the bladder sphincter is sterile. The bacterial microorganism responsible for most cases of bladder inflammation is Escherichia coli (E. coli). This bacterium can migrate from the anus to the urethral opening, then to the bladder, with the possibility of reaching one or both kidneys. Symptoms accompanying cystitis include pain and burning during urination, frequent urination, and pain in the lower abdomen. Additionally, red or dark red discoloration of the urine may occur, indicating hematuria as a result of inflammation of the bladder mucosa. The initial treatment stage involves oral therapy, most often with furazidin. To alleviate symptoms, painkillers or antispasmodics can be additionally introduced. In more severe cases and the course of cystitis, it is recommended to implement an appropriate antibiotic based on the conducted antibiogram. Currently, BPC-157 peptide therapy is used in cystitis complaints.

a. BPC-157 Therapy

The action of peptide BPC-157 exhibits bacteriostatic effects, preventing the multiplication of pathogens. It mobilizes the immune system to fight microorganisms in the urinary tract, which leads to the elimination of inflammation in the bladder and the cure of its inflammation. Additionally, BPC-157 can be used in preventive treatment for recurrent cystitis, eliminating the occurrence of this condition. 

  Nephroprotective action of BPC-157

The concept of nephroprotection

Nephroprotection can be understood in two ways. First, this process concerns the protection of the kidneys, both in a diseased state, when nephroprotective actions prevent the worsening of symptoms, and when they are healthy, through actions preventing the development of diseases and disorders. In the context of nephrology, nephroprotection concerns the plan, both implementation and withdrawal, of drugs and procedures leading to the protection of healthy kidneys and alleviation of symptoms in diseased kidneys. Focusing on the concept of nephroprotection, we can refer to the action profile of the modern therapy of peptide BPC-157. Peptide BPC-157 exhibits both preventive and mitigating nephroprotective effects.

Nephroprotective therapy with BPC-157

The nephroprotective effect of peptide BPC-157 is demonstrated by the example of the toxic effect of cisplatin on the kidneys, a drug used in chemotherapy. Although the peptide cannot be used during cancer treatment, the example of how devastating such therapy is for the kidneys can indicate its nephroprotective effect. In relation to the action of drugs with a milder effect and various damages, it will act even more effectively and safely. Therapy with peptide BPC-157, which shows nephroprotective action, involves reducing proteinuria while preserving glomerular filtration function due to simultaneous dilation of the afferent and efferent arterioles, which prevents an increase in intraglomerular pressure and disturbances in glomerular autoregulation. All of the above processes contribute to the nephroprotective effect of peptide BPC-157.

  Bibliography

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