Toxic Effects of Morphine on the Kidneys in Domestic Rabbits

Morphine is a drug belonging to a group of drugs called opioid painkillers or drugs, which is an opium derivative extracted from the unripe seeds of the opium poppy plant [1]. Morphine relieves severe and moderate pain because of injuries, surgeries, heart attacks or chronic diseases including cancer and it is additionally used as a preoperative treatment to reduce the level of alertness and anxiety [2]. It was first extracted within the city of Paderborn in Germany in the fall of 1803 by Fredrick Sertürner and called it morphine ratio. To the ancient Greek god of dreams Morpheus. Morphine contains in its chemical structure an aromatic ring representing the nucleus of phenanthrene [3]. This ring is connected to several hydrogen coals that take the shape of a boat and stop with the element nitrogen connected to the root of an instance known as piperidine. Studies show that the phenol ring and the piperidine ring are responsible for pain relief events and add to it a penta-ring and hydroxyl radicals (4) was initially used as an analgesic substance, but then it was proven that it can cause addiction and is considered an epidemic of materials Opioids are a public health crisis with inside the United States [5,6,7] and the high dose of Morphine slows the respiratory tract speed, leading to hypoxia and demise, hypotension, drowsiness, vomiting, constipation, severe cough, urinary retention and opioids exert their harmful effects on breathing through activating beta-opioid receptors [8,9]. Oxidative stress and free radicals rise due to the use of morphine [10]. Opioids decrease kidney function by diminishing the renal plasma flow with the drift [11]. The liver and the kidneys are the major organs of metabolism and toxin excretion through urine and feces [12]. This way, the majority of foreign chemicals introduced into the body, such as drugs, are metabolized by hepatocytes and eliminated by renal cells. It is even likely that in the process of metabolism, waste products damage liver and renal cells [13]. Morphine has commercial names, including Oramorph, Cefridol, Morcap and Zomorph [14]. The kidney is the most important part of the urinary device consisting of kidneys, ureters, urinary bladder and urethra The kidneys are characterized in different vertebrates being of similar basic tissue structure in addition to the similarity of the function may be lobed or smooth and different in terms of location and glomeruli and tubules and the degree of complexity and arrangement [15]. The kidney is a glandular organ and there is a pair of them on both sides of the spine and connected to the dorsal wall of the abdomen and their natural color is red-brown that modifications because of the disease and chemicals carried within the blood and its shape as a bean [16].

The structural and functional unit of the mechanism is known as nephrons and there are with inside the human college about (1-1.5) million nephrons in animals, their numbers increase or lower depending on the size and type of animal [17].

Despite the extensive use of morphine as a critical analgesic in medical treatments, limited studies have explored its specific toxic effects on kidney tissues, particularly in animal models such as rabbits. Although earlier studies have largely described systemic effects of opioids, detailed studies of the dose-dependent changes in renal tissue morphologically and functionally are not available. The role of morphine in inducing glomerular degeneration, vascular congestion, tubular cell necrosis and basement membrane detachment has not been thoroughly documented, leaving a gap in understanding the underlying mechanisms of morphine-induced renal toxicity. Moreover, the physiological long-term consequences like weight loss and disruption in metabolism brought about by morphine exposure are not given prominence in existing research.

Study Objective

The present study aims to analyze the toxic effects that are generated by morphine on local rabbit kidney tissues (Oryctolagus cuniculus) using thorough histopathological and physiological evaluations. The experiment explores dose-related changes in renal morphology like glomerular decrease, widening of Bowman's space, vascular engorgement and tubular necrosis after administering morphine subcutaneously for 35 days in doses of 30 mg and 60 mg. Also, the research investigates the impact of morphine on weight and health to reveal systemic effects and changes in metabolism induced by chronic opioid treatment.

This research presents new information regarding the individual histopathological alterations resulting from chronic morphine exposure in renal tissue, a facet of interest not extensively explored through earlier research. While the majority of studies were founded on the renal effects of opioids, this research significantly identifies dose-dependent renal toxicity, including glomerular tightening, necrosis in tubular cells and basement membrane disassociation. Apart from that, the research closes the gap between exposure to morphine and its physiological effects, like marked loss in weight and change in behavior and provides an exhaustive account of the influence of morphine on tissue structure and health.

Working methods

The research was carried out on 21 adult male local rabbits of 1-1.96 kg, bought from local markets in Diyala. The rabbits were kept in a farm under normal conditions in cages with dimensions of 150 × 70 × 50 cm, raised 25 cm above the floor with wire mesh to ensure hygiene and ventilation. The rabbits were divided into three groups and in each group, there were 7 rabbits. The control group was the first group and received a subcutaneous injection of distilled water. The second group was administered a subcutaneous injection of 30 mg of morphine and the third group was given 60 mg of morphine. The injection schedule was repeated for 35 consecutive days to study the morphine exposure effect. All rabbits were sacrificed at the end of the experiment. Rabbit kidneys were carefully dissected and placed in formalin solution for histological analysis [18]. Tissue sections were handled according to routine histopathological protocols to study morphological alterations of kidney tissues. Body weights of the rabbits treated with morphine were also measured pre-experiment and post-experiment to study the effects of morphine on growth and metabolism.

Phenotypic Modifications

The study revealed that rabbits exposed to morphine exhibited several adverse phenotypic changes, including fatigue, lethargy, reduced movement and decreased food intake. Additional symptoms, such as itching, slow breathing and aggression, were particularly evident in the group treated with 60 mg of morphine. The narcotic effect of morphine appears to intensify with increased doses, contributing to more pronounced behavioral changes. The results also demonstrated a significant decrease in body weight across the experimental groups treated with morphine compared to the control group. Rabbits in the 30 mg and 60 mg treatment groups experienced a notable reduction in their mean body weights, as shown in Table 1, with differences statistically significant at the 0.05 level.

Table 1: Effect of morphine on Mean body weight/μm

*Differences are statistically significant at the 0.05 level

These factors collectively underline the significant physiological burden imposed by prolonged morphine exposure, particularly at higher doses. Table 1 summarizes the effect of morphine on the mean body weight of rabbits across three groups: the control group, the 30 mg morphine group and the 60 mg morphine group. The control group exhibited the highest mean body weight (1.37±0.11μm), indicating normal growth and health conditions. In contrast, rabbits treated with 30 mg of morphine showed a significant decrease in mean body weight (0.92±0.09μm) and this reduction was statistically significant (p ≤0.05). The 60 mg group demonstrated the most severe effect, with body weight dropping further, although no standard error is recorded in this table. The mean weight across all 21 rabbits was 0.92±0.43μm.

The Group Injected with 30mg Morphine

Figure 1 shows a transverse section of the kidney tissue from rabbits treated with 30 mg/kg of morphine for 35 days, stained with hematoxylin and eosin (H&E) at 10X magnification. The histological examination reveals notable pathological changes, including vascular congestion, expansion of renal tubular cells and necrosis. The labeled regions highlight significant damage to the renal tubules, with areas marked N indicating tubular cell necrosis, characterized by cell swelling, disintegration and loss of structural integrity.

Figure 1: Transverse section with inside the kidney of rabbits of the group treated with a concentration of 30 mg/kg of morphine for 35 days showing G glomerulus, S cell expansion, N tubule cell necrosis, CO hematogenesis (H&E 10X)

Figure 2 presents another transverse section of the kidney tissue of rabbits treated with 30 mg/kg of morphine for 35 days, stained similarly at 10X magnification. The section highlights additional pathological features, including glomerular contraction (G), edema (E), tubular cell necrosis (N) and hematological congestion (CO). The glomerulus appears severely contracted, suggesting a decline in glomerular cell function and structural integrity. This contraction is associated with Bowman’s space expansion, which disrupts the glomerular filtration process and signifies significant glomerular damage. The edema, marked as E, indicates fluid accumulation in the renal tissue, a common response to cellular injury and oxidative stress.